Home Phytochemical analysis and anticancer activity of the Pithecellobium dulce seed extract in colorectal cancer cells
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Phytochemical analysis and anticancer activity of the Pithecellobium dulce seed extract in colorectal cancer cells

  • Abdullah S. Alhamed EMAIL logo , Mohammed Alqinyah EMAIL logo , Adel F. Alghaith , Mohammad M. Algahtani , Faleh Alqahtani , Fahd A. Nasr , Ali S. Alqahtani , Omar M. Noman , Abdulrahman S. Bazaid , Reem Hussain AlMalki , Anas M. Abdel Rahman , Khalid Alhazzani and Ahmed Z. Alanazi
Published/Copyright: July 20, 2023
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Open Chemistry
From the journal Open Chemistry Volume 21 Issue 1

Abstract

Colorectal cancer remains a challenging medical issue worldwide, and utilizing natural products and plants to produce novel, effective and safe therapies against this disease is continuously a sought-after strategy. Fruit and leaf extracts of Pithecellobium dulce (P. dulce) showed potential anticancer properties as they induced apoptosis of breast cancer and Dalton’s lymphoma ascites cells. Thus, the main objective of the current study is to determine whether the seed extract of P. dulce will affect apoptosis, cell cycle, migration, and inflammation of LoVo colorectal cancer cells. The high-resolution liquid chromatography–mass spectrometry was used to determine the chemical composition of the P. dulce seed extract, which revealed the presence of 35 phytochemicals. The findings of this study indicated a significant cytotoxic effect of seeds of this plant in colorectal cancer characterized by induction of apoptosis, cell cycle arrest, and reduction of migration. In addition, the seed extract suppressed several genes that are essential for cancer progression such as MMP2, MMP9, and IL-8, and, on the other hand, upregulated pro-apoptotic genes such as BAX and P53. This study has established P. dulce as a potential and valuable source for providing future therapies against colorectal cancer and other cancers.

Keywords: Pithecellobium dulce ; colorectal cancer; apoptosis; migration; cytotoxicity

1 Introduction

According to the Centers for Disease Control and Prevention, colorectal cancer is the third most common type of cancer and the third cause of cancer-related deaths in the United States. In 2019, the incidence rate of new colorectal cancer cases per 100,000 people in the United States was 36, of which there were 13 related deaths [1]. These data emphasize the persistent necessity of seeking novel agents and compounds that can aid in the fight against colorectal cancer.

Plants and natural products have always been valuable sources of pharmacological agents that have historically been used in the treatment of a variety of human diseases [2,3,4,5,6]. A prime example of these diseases is cancer as many pharmacological agents that are used against different types of cancer originated from plants [7]. Vincristine, etoposide, irinotecan, and paclitaxel are a few examples of many anticancer drugs that work via different molecular mechanisms but all of them originate from plants [8,9,10,11]. Irinotecan, which is a plant alkaloid, is one of the chemotherapeutic agents that is used to treat metastatic colorectal cancer with resistance to 5-fluorouracil [12].

Pithecellobium dulce (P. dulce) is a tree that can grow up to approximately 15 m in length, has a spiny trunk, and is a member of a flowering plant family called Fabaceae. This plant is native to areas such as South and Central America and India where it is traditionally used for edible and sometimes medicinal purposes [13]. The medicinal purposes of P. dulce are due to the fact that it contains several ingredients known to improve human health. For example, seeds of P. dulce contain antioxidants such as flavonoids, quercetin, and vitamin C as well as several minerals, including calcium, magnesium, and phosphorous [14,15]. Therefore, unsurprisingly, it was shown that this plant has beneficial uses in boosting immune function, strengthening bones and muscles, and managing symptoms of diseases such as dysentery and diabetes [16]. It was reported that the P. dulce leaf extract induced apoptosis of breast cancer cell lines [17]. Similar observations were found in Dalton’s lymphoma ascites (DLA) cells as the fruit extract of P. dulce caused apoptosis of these cancer cells both in vitro and in vivo [18].

Although the role of P. dulce in colorectal cancer is not explored yet, there is sufficient evidence that this type of cancer is responsive to treatment derived from plants like Nux vomica [19], Vitis vinifera, Glycine max, and others [20]. Therefore, this study aims to investigate the role of P. dulce in colorectal cancer. Specifically, the main objective of this project is to determine the phytochemical composition of P. dulce seeds and assess the cytotoxicity of the P. dulce seed extract against colorectal cancer cells. Another objective of this study is to determine the effect of the P. dulce seed extract on migration and inflammation in colorectal cancer cells. Completing the objectives of this study will potentially assist in developing new therapeutic agents of plant origin to treat colorectal cancer.

2 Materials and methods

2.1 Plant collection and authentication

Fresh seeds of P. dulce were collected in May 2020 from Alaflaj province (22.2898579, 46.7188421) in the Riyadh region, Kingdom of Saudi Arabia. The seeds were botanically identified and authenticated by taxonomists at the herbarium of the Botany and Microbiology Department, College of Sciences, King Saud University. A voucher specimen of the seeds was deposited at the Herbarium unit in the College of Sciences, King Saud University (voucher number KSU No. 24593).

2.2 Plant extraction

Seeds of P. dulce were prewashed with distilled water to remove any contaminants and dried in darkness at room temperature for 15 days. The extraction was performed as previously described [21] in which 426 g of dried seeds were milled into a coarse powder using an electrical grinding mill. The coarse powder was then extracted three times by cold maceration in 80% methanol (Sigma-Aldrich, MO, USA) and incubated at room temperature for three days with intermittent shaking to prepare the crude extract. Following extraction, the crude extract was filtered using Whatman filter paper, grade 1 (Wagtech International Ltd, England). The filtrate was then dried using a rotary vacuum evaporator (Buchi Rotavapor R-210, Merck, Darmstadt, Germany) at 45 rpm and 40°C under controlled pressure and then stored in a refrigerator.

2.3 High-resolution liquid chromatography–mass spectrometry analysis

About 60 mg of the dried extract was extracted using MeOH/Acn/dH2O (40:40:20 v/v/v) into small molecules. The high-resolution liquid chromatography–mass spectrometry analysis was carried out using the Waters Acquity UPLC system coupled with a Xevo G2-S QTOF mass spectrometer equipped with an electrospray ionization source (ESI) (Waters Ltd., Elstree, UK) to identify the phytoconstituents of the P. dulce seed extract. The extracted metabolites were then introduced to an ACQUITY UPLC using an XSelect column (100 mm × 2.1 mm, 2.5 μm) (Waters Ltd., Elstree, UK). Mobile phase A (0.1% formic acid in H2O) and mobile phase B (0.1% formic acid in 50% ACN/MeOH) were used. The chromatographic separation was achieved using a gradient elution according to the following conditions: 0–16 min 95–5% A, 16–19 min 5% A, 19–20 min 5–95% A, and 20–22 min 95–95% A, at 300 µL/min flow rate. Positive (ESI+) and negative (ESI−) electrospray ionization modes were used to obtain mass spectra using the following conditions: source temperature (150°C), desolvation temperature (500°C), capillary voltage (3.20 kV), cone voltage (40 V), desolvation gas flow (800.0 L/h), and cone gas flow (50 L/h). The collision energy of both low and high functions was placed at 0 and 10–50 V, respectively, in the MSE mode. Sodium formate (100–1200 Da) was used to calibrate the mass spectrometer. Data were acquired in continuum mode using the Masslynx™ V4.1 workstation (Waters Inc., Milford, MA, USA).

2.4 Metabolites identification

Progenesis QI software (Waters Technologies, Massachusetts, USA) was used to detect peak selection and alignment of detected ions (m/z, Rt). Data were then processed by log transformation, mean centering, and Pareto scaling for univariate analyses. The identified metabolites were putatively annotated based on the following criteria: exact mass, fragmentation pattern, and isotopic distribution search against various databases including the PlantCyc database https://plantcyc.org/, Planta Piloto de Química Fina, Universidad de Alcalá database, NIST database, NIST spectra, and NIST Chemistry WebBook.

2.5 Cell culture

The LoVo cell line (ATCC, USA) was used as a model of colorectal cancer. This cell line is a well-established model of colorectal cancer and has been widely utilized in colorectal cancer research. The human umbilical vein endothelial cells(HUVEC; ATCC, USA) was used as a representative model of normal cells, which were previously established from primary cells isolated from the vein of the human umbilical cord. Other cancer cell lines, MCF7 and A549 (ATCC, USA), were also used to test the effect of the P. dulce extract on other types of cancer. Cells were grown in Dulbecco’s modified Eagle’s medium (Gibco) containing 10% of heat-inactivated fetal bovine serum (Gibco) and 1% of 100× penicillin/streptomycin solution (Gibco) at 37°C and 10% CO2.

2.6 Cell viability analysis

Cell viability of LoVo, HUVECs, MCF7, and A549 treated with different concentrations of the P. dulce seeds extract was evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Additionally, LoVo cells were treated with various concentrations of doxorubicin (MedChemExpress, NJ, USA), which was used as a positive control to compare its cytotoxicity with that of the P. dulce extract. Cells at a density of 1 × 104 cells were seeded on a 96-well plate and cultured for 48 h at a 100 µL cell culture medium. Cells were then treated with five different concentrations of the extract (3.125, 6.25, 12.5, and 25 µg/mL) for 24 h. Following the incubation, MTT dissolved in 1× Dulbecco’s phosphate-buffered saline (PBS) was added to each well and incubated for 3 h at 37°C and 5% CO2 in darkness. After that, the culture medium containing MTT was discarded, and 100 µL of isopropranolol was added to each well to dissolve the purple crystals of formazan. The absorbance at 570 nm for each well was read using a microplate reader (BioTek, Elx-800, Agilent, CA, USA). Dose–response curves for each cell line were plotted, and OriginPro8.5 software was used to generate the half-maximal inhibitory concentration (IC50), which was used in all subsequent experiments.

2.7 Annexin V-FITC/PI apoptosis detection

A FITC Annexin V apoptosis detection kit with propidium iodide (Biolegend, CA, USA) was used to evaluate the total cell death of LoVo cells. About 10 × 104 cells were seeded on 6-well plates overnight and then treated for 24 h. Cells were then harvested and washed twice with ice-cold 1× PBS and then resuspended in 100 µL of Annexin V binding buffer. After that, cells were stained with 5 µL of FITC Annexin V and 5 µL of propidium iodide for 15 min in darkness followed by the addition of 400 µL of Annexin V binding buffer. The stained samples were analyzed using a FACS flow cytometer (Cytomics FC; Beckman Coulter, USA).

2.8 Cell cycle analysis

Cell cycle analysis was carried out according to the manufacturer’s protocol. Briefly, LoVo cells were seeded on 6-well plates at a density of 1 × 105 and incubated overnight followed by treatment for 24 h. Following incubation, cells were collected and washed two times with an ice-cold 1× PBS and then fixed in 70% ethanol for 4 h at 4°C. After fixation, ethanol was discarded and cells were stained with propidium iodide at a concentration of 50 μg/mL for 30 min in darkness. Samples were then analyzed to assess cell cycle stages using a FACS flow cytometer (Cytomics FC; Beckman Coulter, USA).

2.9 Scratch assay

The migration of LoVo cells was assessed using the scratch assay. LoVo cells were cultured on 6-well plates until they reached 80% confluence. Then, a straight-line scratch was created using a sterile 200 μL pipette tip. Cells were then treated for 24 h, and images for the scratch were captured at 0- and 24 h post-scratch using a 4× objective of an EVOS XL Core microscope (Thermofisher, USA). The migration percent was determined by counting the number of migrated cells in the scratched area relative to untreated cells using ImageJ software (NIH Image, Bethesda, MD, USA).

2.10 Quantitative real-time polymerase chain reaction (qPCR)

Total RNA was extracted from LoVo cells treated for 24 h using TRIzol reagent (Invitrogen/Life Technologies, Carlsbad, CA, USA) according to the manufacturer’s protocol. Reverse Transcription Master Mix for qPCR (MedChemExpress, NJ, USA) was used to synthesize cDNA. qPCR was carried out using Low ROX SYBR Green qPCR Master Mix (MedChemExpress, New Jersey, USA). Reverse and forward human primers for BAX, P53, MMP2, MMP9, P21, IL-8, TNF-α, and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) were purchased from Integrated DNA Technologies (Leuven, Belgium), and the sequences of the primers are listed in Table 1. GAPDH was used as a housekeeping gene, and the expression for the gene of interest was normalized to the expression of GAPDH. The relative mRNA expression and the fold difference of the gene expression were calculated using the 2−ΔΔCT method.

Table 1

Forward and reverse primer sequences

No. Gene name Forward primer sequence Reverse primer sequence
1 BAX 5′-GTTTCATCCAGGATCGAGCAG-3′ 5′-CATCTTCTTCCAGATGGTGA-3′
2 P53 5′-CCCCTCCTGGCCCCTGTCATCTTC-3′ 5′-GCAGCGCCTCACAACCTCCGTCAT-3′
3 P21 5′-AGGTGGACCTGGAGACTCTCAG-3′ 5′-TCCTCTTGGAGAAGATCAGCCG-3′
4 MMP2 5′-AGAGACAGTGGATGATGCCTTT-3′ 5′-ATCGTCATCAAAATGGGAGTCT-3′
5 MMP9 5′-GTGCTGGGCTGCTGCTTTGCTG-3′ 5′-GTCGCCCTCAAAGGTTTGGAAT-3′
6 IL-8 5′-AGCCTTCCTGATTTCTGCAG-3′ 5′-GTCCACTCTCAATCACTCTCAG-3′
7 TNF-α 5′-CTCTTCTGCCTGCACTTTG-3′ 5′-ATGGGCTACAGGCTTGTCACTC-3′
8 GAPDH 5′-GCCAAGGTCATCCATGACAACT-3′ 5′-GAGGGGCCATCCACAGTCTT-3′

2.11 Statistical analysis

The statistical analysis was performed using GraphPad Prism 9 Software. Student’s paired t-test was used to determine the statistical difference between the experimental groups, and data were presented as mean ± SD. The value of P < 0.05 was considered statistically significant.

3 Results

3.1 Chemical composition of the P. dulce seed extract

The phytochemicals of the extract were detected using high-resolution liquid chromatography–mass spectrometry with the ultimate goal to determine the constituents with known anticancer properties. The analysis identified 14 phytochemicals in the positive (ESI+) electrospray ionization modes (Table 2; Figure S1) and 21 phytochemicals in the negative (ESI−) electrospray ionization modes (Table 3; Figure S2). Five of these identified phytochemicals have known anticancer properties. Tables 2 and 3 show the retention time, m/z, the average of max abundance, and database ID. Octadecanedioic acid, hydroxystearic acid (HAS), linoelaidic acid, soyasaponin III, and kaempferol 7-O-beta-d-glucopyranoside are the five phytochemical constituents with known anticancer properties [22,23,24,25,26,27,28,29,30].

Table 2

Identified compounds of the P. dulce seed extract on the positive electrospray ionization modes

No. Compound name Retention time (min) m/z Max abundance (%) Database ID
1 2-(Dimethylamino)-6,7-dihydroimidazo[1,2-a] [1,3,5] triazin-4(1H)-one 0.8 146.08 1.03 CSID4524478
2 Pyrimidine, 4,5,6-tris(dimethylamino)- 1.8 174.149 2.73 CSID530712
3 Ethyl N-(2-{1-[N-(butoxycarbonyl)alanyl]-2-pyrrolidinyl}-2-oxo-1-phenylethyl)serylglycinate 7.6 513.27 1.56 CSID479298
4 2-(3,4,5-Trihydroxyphenyl)-3,4,5,7-chromanetetrol 9.6 287.05 2.57 CSID2338991
5 Leucocianidol 10.4 271.06 1.78 CSID64694
6 Bis(2,4-Dimethyl-3-pentanyl) succinate 15.4 279.23 1.18 CSID29758295
7 Octyl 2-tridecyn-1-yl isophthalate 16.1 520.34 10.44 CSID29754019
8 Dodecyl methyl adipate 16.4 293.24 1.63 CSID14278700
9 Pentadecyl phenyl adipate 16.7 496.34 7.05 CSID29742454
10 (3Z)-3-Hexen-1-yl pentadecyl phthalate 16.8 522.3 17.98 CSID29744994
11 3,5-Dimethylphenyl tetradecyl (2E)-2-butenedioate 16.9 480.30 2.06 CSID29741111
12 6-(Tritylamino)hexanenitrile 17.6 319.19 2.31 CSID496483
13 Hexadecyl 4-methylbenzyl glutarate 17.7 524.37 4.77 CSID29761125
14 5-Benzyl-1,4-dimethyl-2,3-diphenylpiperazine 18.4 321.21 1.71 CSID466791
Table 3

Identified compounds of the P. dulce seed extract on the negative electrospray ionization modes

No. Compound name Retention time (min) m/z Max abundance (%) Database ID
1 1(F)-alpha-d-galactosylraffinose 0.80813 665.21 1.60 CSID30785504
2 Methyl 3-O-benzoyl-4,6-O-benzylidene-2-O-[(4-methylphenyl)sulfonyl]hexopyranoside 0.82528 539.13 1.52 CSID496218
3 4-Benzyloxy-2-butenal 2,4-dinitrophenylhydrazone 0.84243 377.08 3.22 CSID7876394
4 7-Deoxydoxorubicinone 0.84243 379.08 1.24 CSID284252
5 beta-(1- > 6)-Galactobiose 0.85957 341.10 2.73 CSID9511747
6 Kaempferol 7-O-beta-d-glucopyranoside 7.37068 447.09 1.05 CSID8270716
7 N-Benzyl-4-{(2E)-2-[4-(diethylamino)-2-methoxybenzylidene]hydrazino}-6-(4-morpholinyl)-1,3,5-triazin-2-amine 7.79933 511.25 1.66 CSID7876456
8 7,8,2′,4′-Tetrahydroxy-isoflavone 8.30812 285.04 3.95 CSID4527133
9 Dihydrotricetin 8.3424 285.04 1.53 CSID4424366
10 Hordatine A 8.95982 571.27 1.04 CSID24632689
11 7,8-Dihydroxy-2-(4-hydroxyphenyl)-4H-chromen-4-one 9.12565 269.04 3.88 CSID600251
12 [(5xi,6beta,7beta,9xi,10xi,13xi,17xi)-20-Ethyl-7,8-dihydroxy-1,6,14,16-tetramethoxyaconitan-4-yl]methyl 2-(3-methyl-2,5-dioxo-1-pyrrolidinyl)benzoate 9.14278 703.31 1.25 CSID4932356
13 Soyasaponin III 14.054 795.45 1.94 CSID10245008
14 2-(8-Hydroxy-1,2,5,5-tetramethyldecahydro-1-naphthalenyl)ethyl acetate 14.3627 295.22 2.80 CSID4926160
15 Allyl tetradecyl carbonate 14.9459 297.24 1.79 CSID4925809
16 9,10-Epoxyoctadecenoic acid 14.9459 295.22 1.12 CSID4861048
17 Palmitoyl lysophosphatidylethanolamine 15.4718 452.27 1.20 CSID80521
18 28-Formylspirosolan-3-yl acetate 15.7119 506.32 1.35 CSID467876
19 1-Oleoyl phosphatidylethanolamine 15.7462 478.29 2.45 CSID7826022
20 Linoelaidic acid 16.6151 279.23 2.10 CSID4445609
21 HAS 17.1753 281.24 4.14 CSID62625

3.2 The effect of the P. dulce seed extract on the cell viability of LoVo cells

The cytotoxic effects of the P. dulce seed extract on the cell viability for LoVo and HUVEC were evaluated using an MTT assay. The extract reduced the cell viability of treated LoVo cells in a concentration-dependent manner, as indicated in Figure 1(a). Extract concentrations of 3.125, 6.25, 12.5, and 25 µg/mL reduced cell viability to 48, 25, 19, and 14%, respectively. Doxorubicin had more cytotoxicity against LoVo cells than the extract (Figure 1(b)). Additionally, the extract exerted a less cytotoxic effect on HUVEC compared to LoVo cells (Figure 1(c)). Based on these data, the IC50 of the extract was determined to be 3.03 ± 0.1 µg/mL. Therefore, 3 µg/mL of the extract was used to conduct all subsequent experiments on LoVo cells to further elucidate the potency and efficacy of this extract. The corresponding IC50 value of the extract against HUVEC was 6.24 ± 0.25 µg/mL. IC50 values of doxorubicin against LoVo and HUVEC were 0.98 ± 0.04 and 2.25 ± 0.12, respectively (Table 4).

Figure 1 The cell viability of the extract-treated LoVo cells (a), doxorubicin-treated LoVo cells (b), and the extract-treated HUVEC (c). LoVo and HUVEC cells were treated with different concentrations of the extract ranging from 3.125 to 25 µg/mL to assess the impact of the extract on cell viability as measured by MTT assay. LoVo cells were also treated with different concentrations of doxorubicin (0.625–5 µg/mL) to compare their cytotoxicity with the extract cytotoxicity. Data were represented as a percentage of cell viability ± SD.
Figure 1

The cell viability of the extract-treated LoVo cells (a), doxorubicin-treated LoVo cells (b), and the extract-treated HUVEC (c). LoVo and HUVEC cells were treated with different concentrations of the extract ranging from 3.125 to 25 µg/mL to assess the impact of the extract on cell viability as measured by MTT assay. LoVo cells were also treated with different concentrations of doxorubicin (0.625–5 µg/mL) to compare their cytotoxicity with the extract cytotoxicity. Data were represented as a percentage of cell viability ± SD.

Table 4

The corresponding IC50 values of the P. dulce seed extract and doxorubicin against LoVo and HUVEC cells

Cell lines and IC50 (μg/mL)
Cell line LoVo HUVEC
P. dulce seeds extract (μg/mL) 3.03 ± 0.1 6.24 ± 0.25
Doxorubicin 0.98 ± 0.04 2.25 ± 0.12

3.3 The P. dulce seed extract-induced apoptosis of LoVo cells

To further investigate the potential cytotoxicity of the extract, the apoptosis rate of LoVo cells was evaluated following treatment with the extract. The extract induced a significant increase in the rate of cell apoptosis in the treated cells (Figure 2(b)). The rates of early and late apoptosis for treated cells were 23 and 16% compared to untreated cells, respectively. The impact of the extract on the apoptosis-related genes P53 and BAX was further evaluated. Extract treatment upregulated the gene expression of P53 and BAX by approximately 2- and 10-fold, respectively (Figure 2(c and d)).

Figure 2 The apoptotic effect of the P. dulce seed extract on LoVo cells. (a) Representative apoptosis histograms for untreated cells and cells treated with the extract following staining with FITC Annexin V and propidium iodide. (b) Percentage of early apoptotic, late apoptotic, and necrotic cells following treatment with the extract as compared to untreated cells. (c) The expression of apoptosis-related gene P53 in treated cells compared to untreated cells. (d) The expression of apoptosis-related gene BAX in treated cells compared to untreated cells. Data were represented as the mean ± SD and P < 0.05 was considered statistically significant.
Figure 2

The apoptotic effect of the P. dulce seed extract on LoVo cells. (a) Representative apoptosis histograms for untreated cells and cells treated with the extract following staining with FITC Annexin V and propidium iodide. (b) Percentage of early apoptotic, late apoptotic, and necrotic cells following treatment with the extract as compared to untreated cells. (c) The expression of apoptosis-related gene P53 in treated cells compared to untreated cells. (d) The expression of apoptosis-related gene BAX in treated cells compared to untreated cells. Data were represented as the mean ± SD and P < 0.05 was considered statistically significant.

3.4 The impact of the P. dulce seeds extract on the cell cycle of LoVo cells

The impact of the extract on cell cycle progression was evaluated for LoVo cells. As shown in Figure 3(b), the treatment with the extract resulted in a significant increase in the cell number at the sub-G1 phase to 27% compared to 0.5% of untreated cells. The increase in the cell number at the sub-G1 phase of the treated cells was accompanied by a decrease in the proportion of cells in the G1, S, and G2-M phases of the cell cycle to 46, 16, and 11%, respectively. Furthermore, the expression of the cell cycle inhibitor P21 gene was significantly upregulated in treated cells as compared to untreated cells (Figure 3(c)).

Figure 3 The impact of the P. dulce seed extract on the cell cycle of LoVo cells. (a) Representative images of cell cycle analysis for untreated cells and cells treated with the extract following staining with propidium iodide. (b) Cell population percentage in cell cycle phases: sub-G1, G1, S, and G2-M in treated cells compared to untreated cells. (c) The gene expression of the cell cycle inhibitor P21 in treated cells compared to untreated cells. Data were represented as the mean ± SD and P < 0.05 was considered statistically significant.
Figure 3

The impact of the P. dulce seed extract on the cell cycle of LoVo cells. (a) Representative images of cell cycle analysis for untreated cells and cells treated with the extract following staining with propidium iodide. (b) Cell population percentage in cell cycle phases: sub-G1, G1, S, and G2-M in treated cells compared to untreated cells. (c) The gene expression of the cell cycle inhibitor P21 in treated cells compared to untreated cells. Data were represented as the mean ± SD and P < 0.05 was considered statistically significant.

3.5 The P. dulce seed extract suppressed the migration of LoVo cells

Scratch assay was used to examine the influence of the extract on cell migration during wound closure of LoVo cells. The results showed a clear decrease in the migration rate of LoVo cells following extract treatment. The quantification of migrated cells revealed that the treatment caused a 78% reduction in the migration rate (Figure 4(b)). The reduction in cell migration was accompanied by a significant downregulation in the gene expression of MMP2 and MMP9 in the treated cells compared to untreated cells (Figure 4(c and d)).

Figure 4 The effect of the P. dulce seeds extract on cell migration in LoVo cells. (a) Representative images of cell migration taken at the beginning of the experiment (0 h) and 24 h post-scratch using 4× objective for untreated cells and cells treated with the extract. (b) Percentage of cell migration rate of cells following treatment with the extract relative to untreated cells. (c) The gene expression of MMP2 following treatment with the extract relative to untreated cells. (d) The gene expression of MMP9 following treatment with the extract relative to untreated cells. Data were represented as the mean ± SD and P < 0.05 was considered statistically significant.
Figure 4

The effect of the P. dulce seeds extract on cell migration in LoVo cells. (a) Representative images of cell migration taken at the beginning of the experiment (0 h) and 24 h post-scratch using 4× objective for untreated cells and cells treated with the extract. (b) Percentage of cell migration rate of cells following treatment with the extract relative to untreated cells. (c) The gene expression of MMP2 following treatment with the extract relative to untreated cells. (d) The gene expression of MMP9 following treatment with the extract relative to untreated cells. Data were represented as the mean ± SD and P < 0.05 was considered statistically significant.

3.6 The P. dulce seed extract modulated the gene expression of inflammatory cytokines in LoVo cells

The next step was to investigate the effect of the P. dulce seed extract on inflammatory signaling as it has been well-established that inflammation plays a crucial role in cancer progression and treatment. To assess the impact of the extract treatment on inflammation, LoVo cells were treated and then the gene expression of two inflammatory cytokines IL-8 and TNF-α was measured. As shown in Figure 5(a), the extract significantly reduced the relative gene expression of IL-8 as compared to untreated cells. Conversely, the TNF-α gene expression was significantly upregulated in the extract-treated cells as compared to the control (Figure 5(b)).

Figure 5 The effect of the P. dulce seed extract on inflammation in LoVo cells. (a) The IL-8 gene expression in the extract-treated cells compared to untreated cells. (b) The TNF-α gene expression in the extract-treated cells compared to untreated cells. Data were represented as the mean ± SD and P < 0.05 was considered statistically significant.
Figure 5

The effect of the P. dulce seed extract on inflammation in LoVo cells. (a) The IL-8 gene expression in the extract-treated cells compared to untreated cells. (b) The TNF-α gene expression in the extract-treated cells compared to untreated cells. Data were represented as the mean ± SD and P < 0.05 was considered statistically significant.

3.7 Exploring the effect of the P. dulce seed extract on cell viability of breast and lung cancer cells

Since several genes that were impacted by P. dulce seeds play roles that are not exclusive to colorectal cancer and can expand to other cancers such as lung and breast cancers, this study opted to determine whether the extract will also affect these cancers. To achieve this aim, MCF7 and A549 cells were treated with various concentrations of the extract to assess their impact on cell viability. The extract reduced the cell viability of both MCF7 and A549 cells in a concentration-dependent manner (Figure 6).

Figure 6 The effect of the P. dulce seed extract on the viability of MCF7 and A549 cells. Cells were exposed to different concentrations of the extract ranging from 3.125 to 25 µg/mL to assess the impact of the extract on cell viability as measured by the MTT assay. Data were represented as a percentage of cell survival ± SD.
Figure 6

The effect of the P. dulce seed extract on the viability of MCF7 and A549 cells. Cells were exposed to different concentrations of the extract ranging from 3.125 to 25 µg/mL to assess the impact of the extract on cell viability as measured by the MTT assay. Data were represented as a percentage of cell survival ± SD.

4 Discussion

Utilizing plants and natural products to produce effective therapies against different types of cancer has proven to be a successful strategy in the past [7]. Fruits and leaves of P. dulce were shown to exert cytotoxic effects in some types of cancer [17,18]. However, the anticancer activity of P. dulce has not been explored in colorectal cancer. Additionally, it remains unknown whether other parts of the P. dulce plant such as seeds will show anticancer activity similar to fruits and leaves. Therefore, this study aimed to further expand the investigation of the role of P. dulce by testing the effect of its seeds on cell viability, apoptosis, migration, and inflammation of colorectal cancer cells.

Identification of phytochemical constituents of the P. dulce seed extract would be necessary to detect phytoconstituents with known anticancer properties and to correlate them with the observed biological activities. Our results revealed the presence of 35 phytochemicals in the methanolic extract of the P. dulce seeds, five of them with known anticancer properties, including octadecanedioic acid, HAS, linoelaidic acid, soyasaponin III, and kaempferol 7-O-beta-d-glucopyranoside. HAS is a long-chain, naturally occurring fatty acid and contains various isomers of HAS. However, in this study, we were not able to differentiate between different isomers of HAS as they have equal molecular masses. Several regioisomers of HAS have been studied for their cytotoxic effects against various types of cancer cells. HAS derivatives such as 5-HAS, 7-HAS, and 9-HAS showed antiproliferative effects against colorectal, prostate, and breast cancer cells [25]. Additionally, in colorectal adenocarcinoma cells (HT29), other studies showed that HAS-9 induced cell cycle arrest G0/G1 via upregulating P21 expression and cell differentiation via inhibition of histone deacetylase 1 [24,27]. Octadecanedioic acid, an, α,ω-dicarboxylic acid, is a natural product that has been found in Pinus radiata and Arabidopsis thaliana. A study reported an improvement in the efficacy of paclitaxel conjugated with octadecanedioic acid as compared to two FDA-approved paclitaxel formulations against the subcutaneous murine xenograft model of human colorectal adenocarcinoma and pancreas ductal carcinoma [26].

The other identified phytochemical, linoleic acid, was found to inhibit the proliferation of colorectal cancer cells. This effect was attributed to the ability of linoleic acid to induce oxidative stress and mitochondrial dysfunction [23]. Another study revealed that linoleic acid suppressed growth and induced apoptosis of gastric and colon cancer cells in a dose-dependent manner along with a decrease in cancer cell invasion in vitro and metastatic foci in the peritoneal cavity in vivo [28]. Soyasaponin III has been shown to inhibit the growth of colorectal adenocarcinoma cells and reduce the activity of protein kinase C activity [29]. Another study reported the proliferation and inhibition of hepatocarcinoma Hep-G1 cells by an extract containing 62% soyasaponin I and 29% soyasaponin III [30]. The other phytochemical identified in the P. dulce seed extract, kaempferol 7-O-beta-d-glucopyranoside, has been shown to exert an antiproliferative effect and induce apoptosis and cell cycle arrest at the G2/M phase against HeLa cervical cancer cells. Indeed, these changes were also associated with the inhibition of NF-κB translocation, upregulation of BAX, downregulation of BCL-2, cyclin B1, and cdk1 [22]. Overall, these data indicated the anticancer activity of these phytochemicals and support the findings of our study about the potential anticancer effect of P. dulce seeds. Additionally, the anticancer activity of other identified phytochemicals has not been tested before and it would be interesting to evaluate their potential cytotoxicity against cancer cells.

The results of this study demonstrated the ability of the P. dulce seed extract to reduce the viability of colorectal cancer cells along with the induction of apoptosis. Furthermore, the extract induced upregulation of BAX and P53, which are known mediators of cell apoptosis. Therefore, these data further supported the assertion of the cytotoxicity of P. dulce seeds. These data are in line with a previous study that showed the potent and selective cytotoxicity of the P. dulce leas extract against breast cancer cells [17]. Dhanisha et al. found that the P. dulce fruit extract had both in vitro and in vivo cytotoxicity against DLA cells [18]. Thus, the results of this study indicated that like the effect of P. dulce fruits and leaves on breast cancer and DLA cells, the seeds of this plant also induced cytotoxicity in colorectal cancer cells.

While other studies focused mainly on the apoptotic effect of P. dulce, this study aimed to expand the investigation to include the effect of this plant on cell cycle and migration. This study demonstrated a substantial elevation in the cell population in the sub-G1 phase; the cells in this phase are recognized by reduced DNA content as a result of DNA fragmentation [31]. The reduction in DNA content is a typical feature of apoptotic cells but it is not clear whether the observed increase in cells at the sub-G1 phase was attributed to the increase in cell apoptosis or was a result of cell cycle arrest of viable cells at the sub-G1 phase. The P21 gene is one of the main regulators of the cell cycle and inhibits cyclin-dependent kinase, thereby arresting the cell cycle and inhibiting cell division [32]. The P. dulce seed extract upregulated the expression of the P21 gene, which might contribute to the effect observed on the cell cycle.

In addition to determining the effect of the P. dulce seed extract on apoptosis and cell cycle progression of colorectal cancer cells, this study also investigated the influence of this plant on the migration of these cells. The findings of the current study revealed that the P. dulce seed extract significantly inhibited the migration of colorectal cancer cells. This result is noteworthy because, to the best of our knowledge, our study is the first to demonstrate the effect of the P. dulce seed extract on the migration of cancer cells. Furthermore, the P. dulce seed extract-induced suppression of migration was accompanied by the downregulation of MMP2 and MMP9 genes. These data would suggest a potential role of the P. dulce seed extract in mitigating colorectal cancer progression since MMP2 and MMP9 have been shown to be critical mediators for cancer migration, invasion, metastasis, and progression.

It is well-established that inflammatory signaling plays a major role in cancer pathophysiology where several inflammatory cytokines such as IL-8 and TNF-α can influence the progression, migration, and apoptosis of different types of cancer, including colorectal cancer [33]. Evidence from a previous study showed that the fruit extract of P. dulce had anti-inflammatory effects, displayed by reducing the expression of multiple cytokines such as IL-1ß and IL-6 [34]. In this study, the P. dulce seed extract suppressed the gene expression of IL-8 in colorectal cancer cells, which concurs with other studies demonstrating an anti-inflammatory role of this plant [34,35]. However, the P. dulce seed extract had the opposite effect on TNF-α as it increased the gene expression of this cytokine. Notably, TNF-α has complex multifaceted roles in cancer pathophysiology where it can induce apoptosis of cancer cells in some cases and promote cancer in others [36]. Therefore, there is a possibility of a dual action of P. dulce where it suppresses the expression of IL-8, thereby contributing to the inhibition of cancer progression, while enhancing the expression of TNF-α, thereby inducing the apoptosis of cancer cells.

Even though the main focus of this study was to evaluate the role of the P. dulce seed extract in colorectal cancer, further investigation was conducted to assess whether the anti-cancer effect of this seed extract is exclusive to colorectal cancer cells or whether it can extend to other cancer. Our findings indicated that while the effect on colorectal cancer cells appeared to be more potent, the P. dulce seed extract induced a reduction in the cell viability of both breast and lung cancer cells. Thus, the seed extract of this plant can have applications beyond its effects on colorectal cancer but further studies to delineate the exact roles of P. dulce seeds in other cancers are warranted.

5 Conclusion

The current study demonstrates the potential anticancer effect of P. dulce seeds on colorectal cancer cells. Indeed, this study further adds to the list of therapeutic benefits of this plant that were already reported, such as enhancing immune function, strengthening bones and muscles, and improving symptoms associated with dysentery and diabetes. Additionally, the findings of this study suggest that P. dulce could potentially be used in cancer therapy as many anticancer agents are developed from plants. Future studies should investigate the molecular mechanisms that mediate these anticancer effects of P. dulce seeds. There is also a need to conduct additional studies that can aid in defining the broader roles of this plant in other types of cancer. Finally, it will be interesting to gauge the value of using P. dulce seeds in combination with classic chemotherapeutic agents to enhance their efficacy and/or to lower their toxicities.

# These authors contributed equally to this work.

Acknowledgements

The authors extend their appreciation to the Deputyship for Research & Innovation, “Ministry of Education” in Saudi Arabia for funding this research (IFKSUOR3-480-1).

  1. Funding information: This research was funded by the Deputyship for Research & Innovation, “Ministry of Education” in Saudi Arabia (project no. IFKSUOR3-480-1).

  2. Author contributions: A.S.H. and M.A.Q. – conceptualization; A.S.H., M.A.Q., A.F.G., M.M.G., F.A.N, A.S.Q, F.A., A.M.A., R.H.A., and O.M.N. – methodology; A.S.H., M.A.Q., F.A.N., A.M.A., R.H.A., and M.M.G. – software; A.S.H., M.A.Q., and A.S.B. – validation; A.S.H., M.A.Q., M.M.G., A.M.A., R.H.A., K.A., A.Z.A., and F.A.N. – formal analysis; A.S.H., M.A.Q., A.F.G., M.M.G, F.A.N., A.M.A., R.H.A., and O.M.N. – investigation; A.S.H., M.A.Q., A.S.Q., K.A., A.Z.A., and A.S.B. – resources; A.S.H., M.A.Q., A.F.G., M.M.G. – data curation; A.S.H. and M.A.Q. – writing and original draft preparation; A.S.H., M.A.Q., A.F.G., K.A., A.Z.A., and M.M.G. – writing, review and editing; A.S.B. – visualization; A.S.H. and M.A.Q. – supervision; A.S.H. and M.A.Q. – project administration; A.S.H. and M.A.Q. – funding acquisition.

  3. Conflict of interest: The authors state no conflict of interest.

  4. Ethical approval: The conducted research is not related to either human or animal use.

  5. Data availability statement: All data generated or analyzed during this study are included in this published article and its supplementary information file.

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Received: 2023-04-05
Revised: 2023-06-28
Accepted: 2023-06-30
Published Online: 2023-07-20

© 2023 the author(s), published by De Gruyter

This work is licensed under the Creative Commons Attribution 4.0 International License.

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  92. Combinatory in silico investigation for potential inhibitors from Curcuma sahuynhensis Škorničk. & N.S. Lý volatile phytoconstituents against influenza A hemagglutinin, SARS-CoV-2 main protease, and Omicron-variant spike protein
  93. Physical, mechanical, and gamma ray shielding properties of the Bi2O3–BaO–B2O3–ZnO–As2O3–MgO–Na2O glass system
  94. Twofold interpenetrated 3D Cd(ii) complex: Crystal structure and luminescent property
  95. Study on the microstructure and soil quality variation of composite soil with soft rock and sand
  96. Ancient spring waters still emerging and accessible in the Roman Forum area: Chemical–physical and microbiological characterization
  97. Extraction and characterization of type I collagen from scales of Mexican Biajaiba fish
  98. Finding small molecular compounds to decrease trimethylamine oxide levels in atherosclerosis by virtual screening
  99. Prefatory in silico studies and in vitro insecticidal effect of Nigella sativa (L.) essential oil and its active compound (carvacrol) against the Callosobruchus maculatus adults (Fab), a major pest of chickpea
  100. Polymerized methyl imidazole silver bromide (CH3C6H5AgBr)6: Synthesis, crystal structures, and catalytic activity
  101. Using calcined waste fish bones as a green solid catalyst for biodiesel production from date seed oil
  102. Influence of the addition of WO3 on TeO2–Na2O glass systems in view of the feature of mechanical, optical, and photon attenuation
  103. Naringin ameliorates 5-fluorouracil elicited neurotoxicity by curtailing oxidative stress and iNOS/NF-ĸB/caspase-3 pathway
  104. GC-MS profile of extracts of an endophytic fungus Alternaria and evaluation of its anticancer and antibacterial potentialities
  105. Green synthesis, chemical characterization, and antioxidant and anti-colorectal cancer effects of vanadium nanoparticles
  106. Determination of caffeine content in coffee drinks prepared in some coffee shops in the local market in Jeddah City, Saudi Arabia
  107. A new 3D supramolecular Cu(ii) framework: Crystal structure and photocatalytic characteristics
  108. Bordeaux mixture accelerates ripening, delays senescence, and promotes metabolite accumulation in jujube fruit
  109. Important application value of injectable hydrogels loaded with omeprazole Schiff base complex in the treatment of pancreatitis
  110. Color tunable benzothiadiazole-based small molecules for lightening applications
  111. Investigation of structural, dielectric, impedance, and mechanical properties of hydroxyapatite-modified barium titanate composites for biomedical applications
  112. Metal gel particles loaded with epidermal cell growth factor promote skin wound repair mechanism by regulating miRNA
  113. In vitro exploration of Hypsizygus ulmarius (Bull.) mushroom fruiting bodies: Potential antidiabetic and anti-inflammatory agent
  114. Alteration in the molecular structure of the adenine base exposed to gamma irradiation: An ESR study
  115. Comprehensive study of optical, thermal, and gamma-ray shielding properties of Bi2O3–ZnO–PbO–B2O3 glasses
  116. Lewis acids as co-catalysts in Pd-based catalyzed systems of the octene-1 hydroethoxycarbonylation reaction
  117. Synthesis, Hirshfeld surface analysis, thermal, and selective α-glucosidase inhibitory studies of Schiff base transition metal complexes
  118. Protective properties of AgNPs green-synthesized by Abelmoschus esculentus on retinal damage on the virtue of its anti-inflammatory and antioxidant effects in diabetic rat
  119. Effects of green decorated AgNPs on lignin-modified magnetic nanoparticles mediated by Cydonia on cecal ligation and puncture-induced sepsis
  120. Treatment of gastric cancer by green mediated silver nanoparticles using Pistacia atlantica bark aqueous extract
  121. Preparation of newly developed porcelain ceramics containing WO3 nanoparticles for radiation shielding applications
  122. Utilization of computational methods for the identification of new natural inhibitors of human neutrophil elastase in inflammation therapy
  123. Some anticancer agents as effective glutathione S-transferase (GST) inhibitors
  124. Clay-based bricks’ rich illite mineral for gamma-ray shielding applications: An experimental evaluation of the effect of pressure rates on gamma-ray attenuation parameters
  125. Stability kinetics of orevactaene pigments produced by Epicoccum nigrum in solid-state fermentation
  126. Treatment of denture stomatitis using iron nanoparticles green-synthesized by Silybum marianum extract
  127. Characterization and antioxidant potential of white mustard (Brassica hirta) leaf extract and stabilization of sunflower oil
  128. Characteristics of Langmuir monomolecular monolayers formed by the novel oil blends
  129. Strategies for optimizing the single GdSrFeO4 phase synthesis
  130. Oleic acid and linoleic acid nanosomes boost immunity and provoke cell death via the upregulation of beta-defensin-4 at genetic and epigenetic levels
  131. Unraveling the therapeutic potential of Bombax ceiba roots: A comprehensive study of chemical composition, heavy metal content, antibacterial activity, and in silico analysis
  132. Green synthesis of AgNPs using plant extract and investigation of its anti-human colorectal cancer application
  133. The adsorption of naproxen on adsorbents obtained from pepper stalk extract by green synthesis
  134. Treatment of gastric cancer by silver nanoparticles encapsulated by chitosan polymers mediated by Pistacia atlantica extract under ultrasound condition
  135. In vitro protective and anti-inflammatory effects of Capparis spinosa and its flavonoids profile
  136. Wear and corrosion behavior of TiC and WC coatings deposited on high-speed steels by electro-spark deposition
  137. Therapeutic effects of green-formulated gold nanoparticles by Origanum majorana on spinal cord injury in rats
  138. Melanin antibacterial activity of two new strains, SN1 and SN2, of Exophiala phaeomuriformis against five human pathogens
  139. Evaluation of the analgesic and anesthetic properties of silver nanoparticles supported over biodegradable acacia gum-modified magnetic nanoparticles
  140. Review Articles
  141. Role and mechanism of fruit waste polyphenols in diabetes management
  142. A comprehensive review of non-alkaloidal metabolites from the subfamily Amaryllidoideae (Amaryllidaceae)
  143. Discovery of the chemical constituents, structural characteristics, and pharmacological functions of Chinese caterpillar fungus
  144. Eco-friendly green approach of nickel oxide nanoparticles for biomedical applications
  145. Advances in the pharmaceutical research of curcumin for oral administration
  146. Rapid Communication
  147. Determination of the contents of bioactive compounds in St. John’s wort (Hypericum perforatum): Comparison of commercial and wild samples
  148. Retraction
  149. Retraction of “Two mixed-ligand coordination polymers based on 2,5-thiophenedicarboxylic acid and flexible N-donor ligands: The protective effect on periodontitis via reducing the release of IL-1β and TNF-α”
  150. Topical Issue on Phytochemicals, biological and toxicological analysis of aromatic medicinal plants
  151. Anti-plasmodial potential of selected medicinal plants and a compound Atropine isolated from Eucalyptus obliqua
  152. Anthocyanin extract from black rice attenuates chronic inflammation in DSS-induced colitis mouse model by modulating the gut microbiota
  153. Evaluation of antibiofilm and cytotoxicity effect of Rumex vesicarius methanol extract
  154. Chemical compositions of Litsea umbellata and inhibition activities
  155. Green synthesis, characterization of silver nanoparticles using Rhynchosia capitata leaf extract and their biological activities
  156. GC-MS analysis and antibacterial activities of some plants belonging to the genus Euphorbia on selected bacterial isolates
  157. The abrogative effect of propolis on acrylamide-induced toxicity in male albino rats: Histological study
  158. A phytoconstituent 6-aminoflavone ameliorates lipopolysaccharide-induced oxidative stress mediated synapse and memory dysfunction via p-Akt/NF-kB pathway in albino mice
  159. Anti-diabetic potentials of Sorbaria tomentosa Lindl. Rehder: Phytochemistry (GC-MS analysis), α-amylase, α-glucosidase inhibitory, in vivo hypoglycemic, and biochemical analysis
  160. Assessment of cytotoxic and apoptotic activities of the Cassia angustifolia aqueous extract against SW480 colon cancer
  161. Biochemical analysis, antioxidant, and antibacterial efficacy of the bee propolis extract (Hymenoptera: Apis mellifera) against Staphylococcus aureus-induced infection in BALB/c mice: In vitro and in vivo study
  162. Assessment of essential elements and heavy metals in Saudi Arabian rice samples underwent various processing methods
  163. Two new compounds from leaves of Capparis dongvanensis (Sy, B. H. Quang & D. V. Hai) and inhibition activities
  164. Hydroxyquinoline sulfanilamide ameliorates STZ-induced hyperglycemia-mediated amyleoid beta burden and memory impairment in adult mice
  165. An automated reading of semi-quantitative hemagglutination results in microplates: Micro-assay for plant lectins
  166. Inductively coupled plasma mass spectrometry assessment of essential and toxic trace elements in traditional spices consumed by the population of the Middle Eastern region in their recipes
  167. Phytochemical analysis and anticancer activity of the Pithecellobium dulce seed extract in colorectal cancer cells
  168. Impact of climatic disturbances on the chemical compositions and metabolites of Salvia officinalis
  169. Physicochemical characterization, antioxidant and antifungal activities of essential oils of Urginea maritima and Allium sativum
  170. Phytochemical analysis and antifungal efficiency of Origanum majorana extracts against some phytopathogenic fungi causing tomato damping-off diseases
  171. Special Issue on 4th IC3PE
  172. Graphene quantum dots: A comprehensive overview
  173. Studies on the intercalation of calcium–aluminium layered double hydroxide-MCPA and its controlled release mechanism as a potential green herbicide
  174. Synergetic effect of adsorption and photocatalysis by zinc ferrite-anchored graphitic carbon nitride nanosheet for the removal of ciprofloxacin under visible light irradiation
  175. Exploring anticancer activity of the Indonesian guava leaf (Psidium guajava L.) fraction on various human cancer cell lines in an in vitro cell-based approach
  176. The comparison of gold extraction methods from the rock using thiourea and thiosulfate
  177. Special Issue on Marine environmental sciences and significance of the multidisciplinary approaches
  178. Sorption of alkylphenols and estrogens on microplastics in marine conditions
  179. Cytotoxic ketosteroids from the Red Sea soft coral Dendronephthya sp.
  180. Antibacterial and biofilm prevention metabolites from Acanthophora spicifera
  181. Characteristics, source, and health risk assessment of aerosol polyaromatic hydrocarbons in the rural and urban regions of western Saudi Arabia
  182. Special Issue on Advanced Nanomaterials for Energy, Environmental and Biological Applications - Part II
  183. Green synthesis, characterization, and evaluation of antibacterial activities of cobalt nanoparticles produced by marine fungal species Periconia prolifica
  184. Combustion-mediated sol–gel preparation of cobalt-doped ZnO nanohybrids for the degradation of acid red and antibacterial performance
  185. Perinatal supplementation with selenium nanoparticles modified with ascorbic acid improves hepatotoxicity in rat gestational diabetes
  186. Evaluation and chemical characterization of bioactive secondary metabolites from endophytic fungi associated with the ethnomedicinal plant Bergenia ciliata
  187. Enhancing photovoltaic efficiency with SQI-Br and SQI-I sensitizers: A comparative analysis
  188. Nanostructured p-PbS/p-CuO sulfide/oxide bilayer heterojunction as a promising photoelectrode for hydrogen gas generation
https://doi.org/10.1515/chem-2023-0362
Keywords for this article
Pithecellobium dulce; colorectal cancer; apoptosis; migration; cytotoxicity
Creative Commons
BY 4.0

Articles in the same Issue

  1. Characteristics, source, and health risk assessment of aerosol polyaromatic hydrocarbons in the rural and urban regions of western Saudi Arabia
  2. Regular Articles
  3. A network-based correlation research between element electronegativity and node importance
  4. Pomegranate attenuates kidney injury in cyclosporine-induced nephrotoxicity in rats by suppressing oxidative stress
  5. Ab initio study of fundamental properties of XInO3 (X = K, Rb, Cs) perovskites
  6. Responses of feldspathic sandstone and sand-reconstituted soil C and N to freeze–thaw cycles
  7. Robust fractional control based on high gain observers design (RNFC) for a Spirulina maxima culture interfaced with an advanced oxidation process
  8. Study on arsenic speciation and redistribution mechanism in Lonicera japonica plants via synchrotron techniques
  9. Optimization of machining Nilo 36 superalloy parameters in turning operation
  10. Vacuum impregnation pre-treatment: A novel method for incorporating mono- and divalent cations into potato strips to reduce the acrylamide formation in French fries
  11. Characterization of effective constituents in Acanthopanax senticosus fruit for blood deficiency syndrome based on the chinmedomics strategy
  12. Comparative analysis of the metabolites in Pinellia ternata from two producing regions using ultra-high-performance liquid chromatography–electrospray ionization–tandem mass spectrometry
  13. The assessment of environmental parameter along the desalination plants in the Kingdom of Saudi Arabia
  14. Effects of harpin and carbendazim on antioxidant accumulation in young jujube leaves
  15. The effects of in ovo injected with sodium borate on hatching performance and small intestine morphology in broiler chicks
  16. Optimization of cutting forces and surface roughness via ANOVA and grey relational analysis in machining of In718
  17. Essential oils of Origanum compactum Benth: Chemical characterization, in vitro, in silico, antioxidant, and antibacterial activities
  18. Translocation of tungsten(vi) oxide/gadolinium(iii) fluoride in tellurite glasses towards improvement of gamma-ray attenuation features in high-density glass shields
  19. Mechanical properties, elastic moduli, and gamma ray attenuation competencies of some TeO2–WO3–GdF3 glasses: Tailoring WO3–GdF3 substitution toward optimum behavioral state range
  20. Comparison between the CIDR or sponge with hormone injection to induce estrus synchronization for twining and sex preselection in Naimi sheep
  21. Exergetic performance analyses of three different cogeneration plants
  22. Psoralea corylifolia (babchi) seeds enhance proliferation of normal human cultured melanocytes: GC–MS profiling and biological investigation
  23. A novel electrochemical micro-titration method for quantitative evaluation of the DPPH free radical scavenging capacity of caffeic acid
  24. Comparative study between supported bimetallic catalysts for nitrate remediation in water
  25. Persicaline, an alkaloid from Salvadora persica, inhibits proliferation and induces apoptosis and cell-cycle arrest in MCF-7 cells
  26. Determination of nicotine content in locally produced smokeless tobacco (Shammah) samples from Jazan region of Saudi Arabia using a convenient HPLC-MS/MS method
  27. Changes in oxidative stress markers in pediatric burn injury over a 1-week period
  28. Integrated geophysical techniques applied for petroleum basins structural characterization in the central part of the Western Desert, Egypt
  29. The impact of chemical modifications on gamma-ray attenuation properties of some WO3-reinforced tellurite glasses
  30. Microwave and Cs+-assisted chemo selective reaction protocol for synthesizing 2-styryl quinoline biorelevant molecules
  31. Structural, physical, and radiation absorption properties of a significant nuclear power plant component: A comparison between REX-734 and 316L SS austenitic stainless steels
  32. Effect of Moringa oleifera on serum YKL-40 level: In vivo rat periodontitis model
  33. Investigating the impact of CO2 emissions on the COVID-19 pandemic by generalized linear mixed model approach with inverse Gaussian and gamma distributions
  34. Influence of WO3 content on gamma rays attenuation characteristics of phosphate glasses at low energy range
  35. Study on CO2 absorption performance of ternary DES formed based on DEA as promoting factor
  36. Performance analyses of detonation engine cogeneration cycles
  37. Sterols from Centaurea pumilio L. with cell proliferative activity: In vitro and in silico studies
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  41. Optimization of ultra-high pressure-assisted extraction of total phenols from Eucommia ulmoides leaves by response surface methodology
  42. Harpin enhances antioxidant nutrient accumulation and decreases enzymatic browning in stored soybean sprouts
  43. Physicochemical and biological properties of carvacrol
  44. Radix puerariae in the treatment of diabetic nephropathy: A network pharmacology analysis and experimental validation
  45. Anti-Alzheimer, antioxidants, glucose-6-phosphate dehydrogenase effects of Taverniera glabra mediated ZnO and Fe2O3 nanoparticles in alloxan-induced diabetic rats
  46. Experimental study on photocatalytic CO2 reduction performance of ZnS/CdS-TiO2 nanotube array thin films
  47. Epoxy-reinforced heavy metal oxides for gamma ray shielding purposes
  48. Black mulberry (Morus nigra L.) fruits: As a medicinal plant rich in human health-promoting compounds
  49. Promising antioxidant and antimicrobial effects of essential oils extracted from fruits of Juniperus thurifera: In vitro and in silico investigations
  50. Chloramine-T-induced oxidation of Rizatriptan Benzoate: An integral chemical and spectroscopic study of products, mechanisms and kinetics
  51. Study on antioxidant and antimicrobial potential of chemically profiled essential oils extracted from Juniperus phoenicea (L.) by use of in vitro and in silico approaches
  52. Screening and characterization of fungal taxol-producing endophytic fungi for evaluation of antimicrobial and anticancer activities
  53. Mineral composition, principal polyphenolic components, and evaluation of the anti-inflammatory, analgesic, and antioxidant properties of Cytisus villosus Pourr leaf extracts
  54. In vitro antiproliferative efficacy of Annona muricata seed and fruit extracts on several cancer cell lines
  55. An experimental study for chemical characterization of artificial anterior cruciate ligament with coated chitosan as biomaterial
  56. Prevalence of residual risks of the transfusion-transmitted infections in Riyadh hospitals: A two-year retrospective study
  57. Computational and experimental investigation of antibacterial and antifungal properties of Nicotiana tabacum extracts
  58. Reinforcement of cementitious mortars with hemp fibers and shives
  59. X-ray shielding properties of bismuth-borate glass doped with rare earth ions
  60. Green supported silver nanoparticles over modified reduced graphene oxide: Investigation of its antioxidant and anti-ovarian cancer effects
  61. Orthogonal synthesis of a versatile building block for dual functionalization of targeting vectors
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  67. Screening and optimization of extracellular pectinase produced by Bacillus thuringiensis SH7
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  69. Synergistic effects of harpin and NaCl in determining soybean sprout quality under non-sterile conditions
  70. Field evaluation of different eco-friendly alternative control methods against Panonychus citri [Acari: Tetranychidae] spider mite and its predators in citrus orchards
  71. Exploring the antimicrobial potential of biologically synthesized zero valent iron nanoparticles
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  74. A novel statistical modeling of air pollution and the COVID-19 pandemic mortality data by Poisson, geometric, and negative binomial regression models with fixed and random effects
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  76. An alternative approach for the excess lifetime cancer risk and prediction of radiological parameters
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  78. Study of hydrolysis and production of instant ginger (Zingiber officinale) tea
  79. Novel green synthesis of zinc oxide nanoparticles using Salvia rosmarinus extract for treatment of human lung cancer
  80. Evaluation of second trimester plasma lipoxin A4, VEGFR-1, IL-6, and TNF-α levels in pregnant women with gestational diabetes mellitus
  81. Antidiabetic, antioxidant and cytotoxicity activities of ortho- and para-substituted Schiff bases derived from metformin hydrochloride: Validation by molecular docking and in silico ADME studies
  82. Antioxidant, antidiabetic, antiglaucoma, and anticholinergic effects of Tayfi grape (Vitis vinifera): A phytochemical screening by LC-MS/MS analysis
  83. Identification of genetic polymorphisms in the stearoyl CoA desaturase gene and its association with milk quality traits in Najdi sheep
  84. Cold-acclimation effect on cadmium absorption and biosynthesis of polyphenolics, and free proline and photosynthetic pigments in Spirogyra aequinoctialis
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  86. Nanoarchitectonics and performance evaluation of a Fe3O4-stabilized Pickering emulsion-type differential pressure plugging agent
  87. Investigating pyrolysis characteristics of Shengdong coal through Py-GC/MS
  88. Extraction, phytochemical characterization, and antifungal activity of Salvia rosmarinus extract
  89. Introducing a novel and natural antibiotic for the treatment of oral pathogens: Abelmoschus esculentus green-formulated silver nanoparticles
  90. Optimization of gallic acid-enriched ultrasonic-assisted extraction from mango peels
  91. Effect of gamma rays irradiation in the structure, optical, and electrical properties of samarium doped bismuth titanate ceramics
  92. Combinatory in silico investigation for potential inhibitors from Curcuma sahuynhensis Škorničk. & N.S. Lý volatile phytoconstituents against influenza A hemagglutinin, SARS-CoV-2 main protease, and Omicron-variant spike protein
  93. Physical, mechanical, and gamma ray shielding properties of the Bi2O3–BaO–B2O3–ZnO–As2O3–MgO–Na2O glass system
  94. Twofold interpenetrated 3D Cd(ii) complex: Crystal structure and luminescent property
  95. Study on the microstructure and soil quality variation of composite soil with soft rock and sand
  96. Ancient spring waters still emerging and accessible in the Roman Forum area: Chemical–physical and microbiological characterization
  97. Extraction and characterization of type I collagen from scales of Mexican Biajaiba fish
  98. Finding small molecular compounds to decrease trimethylamine oxide levels in atherosclerosis by virtual screening
  99. Prefatory in silico studies and in vitro insecticidal effect of Nigella sativa (L.) essential oil and its active compound (carvacrol) against the Callosobruchus maculatus adults (Fab), a major pest of chickpea
  100. Polymerized methyl imidazole silver bromide (CH3C6H5AgBr)6: Synthesis, crystal structures, and catalytic activity
  101. Using calcined waste fish bones as a green solid catalyst for biodiesel production from date seed oil
  102. Influence of the addition of WO3 on TeO2–Na2O glass systems in view of the feature of mechanical, optical, and photon attenuation
  103. Naringin ameliorates 5-fluorouracil elicited neurotoxicity by curtailing oxidative stress and iNOS/NF-ĸB/caspase-3 pathway
  104. GC-MS profile of extracts of an endophytic fungus Alternaria and evaluation of its anticancer and antibacterial potentialities
  105. Green synthesis, chemical characterization, and antioxidant and anti-colorectal cancer effects of vanadium nanoparticles
  106. Determination of caffeine content in coffee drinks prepared in some coffee shops in the local market in Jeddah City, Saudi Arabia
  107. A new 3D supramolecular Cu(ii) framework: Crystal structure and photocatalytic characteristics
  108. Bordeaux mixture accelerates ripening, delays senescence, and promotes metabolite accumulation in jujube fruit
  109. Important application value of injectable hydrogels loaded with omeprazole Schiff base complex in the treatment of pancreatitis
  110. Color tunable benzothiadiazole-based small molecules for lightening applications
  111. Investigation of structural, dielectric, impedance, and mechanical properties of hydroxyapatite-modified barium titanate composites for biomedical applications
  112. Metal gel particles loaded with epidermal cell growth factor promote skin wound repair mechanism by regulating miRNA
  113. In vitro exploration of Hypsizygus ulmarius (Bull.) mushroom fruiting bodies: Potential antidiabetic and anti-inflammatory agent
  114. Alteration in the molecular structure of the adenine base exposed to gamma irradiation: An ESR study
  115. Comprehensive study of optical, thermal, and gamma-ray shielding properties of Bi2O3–ZnO–PbO–B2O3 glasses
  116. Lewis acids as co-catalysts in Pd-based catalyzed systems of the octene-1 hydroethoxycarbonylation reaction
  117. Synthesis, Hirshfeld surface analysis, thermal, and selective α-glucosidase inhibitory studies of Schiff base transition metal complexes
  118. Protective properties of AgNPs green-synthesized by Abelmoschus esculentus on retinal damage on the virtue of its anti-inflammatory and antioxidant effects in diabetic rat
  119. Effects of green decorated AgNPs on lignin-modified magnetic nanoparticles mediated by Cydonia on cecal ligation and puncture-induced sepsis
  120. Treatment of gastric cancer by green mediated silver nanoparticles using Pistacia atlantica bark aqueous extract
  121. Preparation of newly developed porcelain ceramics containing WO3 nanoparticles for radiation shielding applications
  122. Utilization of computational methods for the identification of new natural inhibitors of human neutrophil elastase in inflammation therapy
  123. Some anticancer agents as effective glutathione S-transferase (GST) inhibitors
  124. Clay-based bricks’ rich illite mineral for gamma-ray shielding applications: An experimental evaluation of the effect of pressure rates on gamma-ray attenuation parameters
  125. Stability kinetics of orevactaene pigments produced by Epicoccum nigrum in solid-state fermentation
  126. Treatment of denture stomatitis using iron nanoparticles green-synthesized by Silybum marianum extract
  127. Characterization and antioxidant potential of white mustard (Brassica hirta) leaf extract and stabilization of sunflower oil
  128. Characteristics of Langmuir monomolecular monolayers formed by the novel oil blends
  129. Strategies for optimizing the single GdSrFeO4 phase synthesis
  130. Oleic acid and linoleic acid nanosomes boost immunity and provoke cell death via the upregulation of beta-defensin-4 at genetic and epigenetic levels
  131. Unraveling the therapeutic potential of Bombax ceiba roots: A comprehensive study of chemical composition, heavy metal content, antibacterial activity, and in silico analysis
  132. Green synthesis of AgNPs using plant extract and investigation of its anti-human colorectal cancer application
  133. The adsorption of naproxen on adsorbents obtained from pepper stalk extract by green synthesis
  134. Treatment of gastric cancer by silver nanoparticles encapsulated by chitosan polymers mediated by Pistacia atlantica extract under ultrasound condition
  135. In vitro protective and anti-inflammatory effects of Capparis spinosa and its flavonoids profile
  136. Wear and corrosion behavior of TiC and WC coatings deposited on high-speed steels by electro-spark deposition
  137. Therapeutic effects of green-formulated gold nanoparticles by Origanum majorana on spinal cord injury in rats
  138. Melanin antibacterial activity of two new strains, SN1 and SN2, of Exophiala phaeomuriformis against five human pathogens
  139. Evaluation of the analgesic and anesthetic properties of silver nanoparticles supported over biodegradable acacia gum-modified magnetic nanoparticles
  140. Review Articles
  141. Role and mechanism of fruit waste polyphenols in diabetes management
  142. A comprehensive review of non-alkaloidal metabolites from the subfamily Amaryllidoideae (Amaryllidaceae)
  143. Discovery of the chemical constituents, structural characteristics, and pharmacological functions of Chinese caterpillar fungus
  144. Eco-friendly green approach of nickel oxide nanoparticles for biomedical applications
  145. Advances in the pharmaceutical research of curcumin for oral administration
  146. Rapid Communication
  147. Determination of the contents of bioactive compounds in St. John’s wort (Hypericum perforatum): Comparison of commercial and wild samples
  148. Retraction
  149. Retraction of “Two mixed-ligand coordination polymers based on 2,5-thiophenedicarboxylic acid and flexible N-donor ligands: The protective effect on periodontitis via reducing the release of IL-1β and TNF-α”
  150. Topical Issue on Phytochemicals, biological and toxicological analysis of aromatic medicinal plants
  151. Anti-plasmodial potential of selected medicinal plants and a compound Atropine isolated from Eucalyptus obliqua
  152. Anthocyanin extract from black rice attenuates chronic inflammation in DSS-induced colitis mouse model by modulating the gut microbiota
  153. Evaluation of antibiofilm and cytotoxicity effect of Rumex vesicarius methanol extract
  154. Chemical compositions of Litsea umbellata and inhibition activities
  155. Green synthesis, characterization of silver nanoparticles using Rhynchosia capitata leaf extract and their biological activities
  156. GC-MS analysis and antibacterial activities of some plants belonging to the genus Euphorbia on selected bacterial isolates
  157. The abrogative effect of propolis on acrylamide-induced toxicity in male albino rats: Histological study
  158. A phytoconstituent 6-aminoflavone ameliorates lipopolysaccharide-induced oxidative stress mediated synapse and memory dysfunction via p-Akt/NF-kB pathway in albino mice
  159. Anti-diabetic potentials of Sorbaria tomentosa Lindl. Rehder: Phytochemistry (GC-MS analysis), α-amylase, α-glucosidase inhibitory, in vivo hypoglycemic, and biochemical analysis
  160. Assessment of cytotoxic and apoptotic activities of the Cassia angustifolia aqueous extract against SW480 colon cancer
  161. Biochemical analysis, antioxidant, and antibacterial efficacy of the bee propolis extract (Hymenoptera: Apis mellifera) against Staphylococcus aureus-induced infection in BALB/c mice: In vitro and in vivo study
  162. Assessment of essential elements and heavy metals in Saudi Arabian rice samples underwent various processing methods
  163. Two new compounds from leaves of Capparis dongvanensis (Sy, B. H. Quang & D. V. Hai) and inhibition activities
  164. Hydroxyquinoline sulfanilamide ameliorates STZ-induced hyperglycemia-mediated amyleoid beta burden and memory impairment in adult mice
  165. An automated reading of semi-quantitative hemagglutination results in microplates: Micro-assay for plant lectins
  166. Inductively coupled plasma mass spectrometry assessment of essential and toxic trace elements in traditional spices consumed by the population of the Middle Eastern region in their recipes
  167. Phytochemical analysis and anticancer activity of the Pithecellobium dulce seed extract in colorectal cancer cells
  168. Impact of climatic disturbances on the chemical compositions and metabolites of Salvia officinalis
  169. Physicochemical characterization, antioxidant and antifungal activities of essential oils of Urginea maritima and Allium sativum
  170. Phytochemical analysis and antifungal efficiency of Origanum majorana extracts against some phytopathogenic fungi causing tomato damping-off diseases
  171. Special Issue on 4th IC3PE
  172. Graphene quantum dots: A comprehensive overview
  173. Studies on the intercalation of calcium–aluminium layered double hydroxide-MCPA and its controlled release mechanism as a potential green herbicide
  174. Synergetic effect of adsorption and photocatalysis by zinc ferrite-anchored graphitic carbon nitride nanosheet for the removal of ciprofloxacin under visible light irradiation
  175. Exploring anticancer activity of the Indonesian guava leaf (Psidium guajava L.) fraction on various human cancer cell lines in an in vitro cell-based approach
  176. The comparison of gold extraction methods from the rock using thiourea and thiosulfate
  177. Special Issue on Marine environmental sciences and significance of the multidisciplinary approaches
  178. Sorption of alkylphenols and estrogens on microplastics in marine conditions
  179. Cytotoxic ketosteroids from the Red Sea soft coral Dendronephthya sp.
  180. Antibacterial and biofilm prevention metabolites from Acanthophora spicifera
  181. Characteristics, source, and health risk assessment of aerosol polyaromatic hydrocarbons in the rural and urban regions of western Saudi Arabia
  182. Special Issue on Advanced Nanomaterials for Energy, Environmental and Biological Applications - Part II
  183. Green synthesis, characterization, and evaluation of antibacterial activities of cobalt nanoparticles produced by marine fungal species Periconia prolifica
  184. Combustion-mediated sol–gel preparation of cobalt-doped ZnO nanohybrids for the degradation of acid red and antibacterial performance
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