Home Cymbopogon proximus phytochemicals induce S-phase arrest in A549 lung cancer cell lines via CDK2/cyclin A2 inhibition: gas chromatography-mass spectrometry and molecular docking analyses
Article
Licensed
Unlicensed Requires Authentication

Cymbopogon proximus phytochemicals induce S-phase arrest in A549 lung cancer cell lines via CDK2/cyclin A2 inhibition: gas chromatography-mass spectrometry and molecular docking analyses

  • Noha A. Seif-Eldein ORCID logo , Salwa A. Abu El Wafa ORCID logo EMAIL logo , Esraa Z. Mohammed and Abeer Temraz
Published/Copyright: May 24, 2024
Become an author with De Gruyter Brill
Submit Manuscript Author Information
Zeitschrift für Naturforschung C
From the journal Zeitschrift für Naturforschung C Volume 79 Issue 9-10

Abstract

Cymbopogon proximus comprises several phytoconstituent classes that are reported to possess anticancer activity; however, studies on the anticancer potentials of the plant are lacking. C. proximus was extracted using solvents with increasing polarity. In-vitro cytotoxic activity of C. proximus extracts was examined against liver (HepG2), lung (A549), prostate (PC3), and bone (MG63) cell lines using MTT assay in comparison to doxorubicin. Flow cytometry was used to analyze the cell cycle for identification of the phase of inhibition. Chemical composition of the most active fraction was examined using the GC/MS technique. Molecular docking was used to explore the mechanism of cytotoxicity against A549, and the results were confirmed by Western blot analysis. Petroleum ether fraction was the highly effective fraction against A549 with IC50 = 14.02 ± 2.79. GC/MS analysis of Pet.Eth led to the identification of nine compounds in unsaponifiable matter and 27 components in the saponifiable fraction. Di-N-octyl phthalate, 3-β-hydroxylean-11.13(18)-dien-30-oic acid methyl ester, elemol hydrocarbons, linoelaidic acid and linoleic acid demonstrated the lowest docking binding scores and similar binding modes against CDK2 as compared to that attained by the native ligand R-Roscovitine “CDK2 ATP inhibitor”. Western blot analysis demonstrated that CDK2/cyclinA2 protein expression has been suppressed in A549 cell lines by Pet.Eth fraction.

Keywords: Cymbopogon proximus ; halfabar; lung cancer; in silico study; western blot
Corresponding author: Salwa A. Abu El Wafa, Pharmacognosy and Medicinal Plants Department, Faculty of Pharmacy for Girls, Al Azhar University, Cairo, Egypt, E-mail:

Acknowledgments

The authors gratefully acknowledge Dr Hanan M. Alharbi, assistant professor at Department of Pharmaceutics, Faculty of Pharmacy, Umm Al-Qura University, Saudi Arabia for her assistance in editing the manuscript.

  1. Research ethics: The techniques were performed according to the ethical standards and guidelines of the animal care and use committee at the Faculty of Pharmacy, Al Azhar University, Egypt (404).

  2. Author contributions: Conceptualization, N.A.S., S.A.A., and A.T.; methodology, N.A.S., S.A.A., and A.T.; writing – original draft preparation, N.A.S., S.A.A., E.Z.M., and A.T.; formal analysis, E.Z.M., N.A.S., and S.A.A.; supervision, A.T.; review. All authors have read and agreed to the published version of the manuscript.

  3. Competing interests: The authors declare no conflict of interest.

  4. Research funding: This research received no external funding.

  5. Data availability: The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request. .

References

1. Haris, M, Mahmood, RI, Rahman, HA, Rahman, NA. In vitro cytotoxic activity of Clerodendrum infortunatum L. against T47D, PC-3, A549 and HCT-116 human cancer cell lines and its phytochemical screening. Int J Pharm Pharmaceut Sci 2016;8:439–4.Search in Google Scholar

2. Barta, JA, Powell, CA, Wisnivesky, JP. Global epidemiology of lung cancer. Ann Glob Health 2019;85:8. https://doi.org/10.5334%2Faogh.2419.10.5334/aogh.2419Search in Google Scholar PubMed PubMed Central

3. Van Rijt, SH, Romero-Canelón, I, Fu, Y, Shnyder, SD, Sadler, PJ. Potent organometallic osmium compounds induce mitochondria-mediated apoptosis and S-phase cell cycle arrest in A549 non-small cell lung cancer cells. Metallomics 2014;6:1014–22. https://doi.org/10.1039/c4mt00034j.Search in Google Scholar PubMed

4. Tadesse, S, Anshabo, AT, Portman, N, Lim, E, Tilley, W, Caldon, CE, et al.. Targeting CDK2 in cancer: challenges and opportunities for therapy. Drug Discov Today 2020;25:406–13. https://doi.org/10.1016/j.drudis.2019.12.001.Search in Google Scholar PubMed

5. Malin, MA, Ali, MM, Ramadhani, AM. GC-MS analysis and antimicrobial activities of C. proximus essential oil and phytochemical screening of its crude extracts. J Med Plants 2018;6:117–22.Search in Google Scholar

6. Gaba, J, Bhardwaj, G, Sharma, A. Lemongrass. In: Antioxidants in vegetables and nuts-properties and health benefits, 1st ed. Singapore: Springer; 2020:75–103 pp.10.1007/978-981-15-7470-2_4Search in Google Scholar

7. Althurwi, HN, Abdel-Kader, MS, Alharthy, KM, Salkini, MA, Albaqami, FF. Cymbopogon proximus essential oil protects rats against isoproterenol-induced cardiac hypertrophy and fibrosis. Molecules 2020;25:1786. https://doi.org/10.3390/molecules25081786.Search in Google Scholar PubMed PubMed Central

8. El-Askary, HI, Meselhy, MR, Galal, AM. Sesquiterpenes from Cymbopogon proximus. Molecules 2003;8:670–7. https://doi.org/10.3390/80900670.Search in Google Scholar

9. Ibrahim, FY, El-Khateeb, AY. Effect of herbal beverages of Foeniculum vulgare and Cymbopogon proximus on inhibition of calcium oxalate renal crystals formation in rats. Ann Agric Sci 2013;58:221–9. https://doi.org/10.1016/j.aoas.2013.07.006.Search in Google Scholar

10. Sharma, PR, Mondhe, DM, Muthiah, S, Pal, HC, Shahi, AK, Saxena, AK, et al.. Anticancer activity of an essential oil from Cymbopogon flexuosus. Chem Biol Interact 2009;179:160–8. https://doi.org/10.1016/j.cbi.2008.12.004.Search in Google Scholar PubMed

11. Pereira, GL, Almeida, TC, Seibert, JB, Amparo, TR, Soares, RD, Rodrigues, IV, et al.. Antitumor effect of Cymbopogon densiflorus (Linneu) essential oil in bladder cancer cells. Nat Prod Res 2021;35:5238–42. https://doi.org/10.1080/14786419.2020.1747453.Search in Google Scholar PubMed

12. Sayed, HK, Issa, MA, Mahmoud, ME, Ismail, HA, Hassan, EA, Darwish, AG. Cytotoxic activities of Cymbopogon citratus extracts against three different human cancer cell lines: lung carcinoma (A549), breast cancer (MCF-7) and hepatocellular carcinoma (Hep G2). JMR 2022;4:21–6. https://doi.org/10.21608/jmr.2021.90284.1081.Search in Google Scholar

13. Bahuguna, A, Khan, I, Bajpai, VK, Kang, SC. MTT assay to evaluate the cytotoxic potential of a drug. Bangladesh J Pharmacol 2017;12:115–18. https://doi.org/10.3329/bjp.v12i2.30892.Search in Google Scholar

14. Pozarowski, P, Darzynkiewicz, Z. Analysis of cell cycle by flow cytometry. In: Checkpoint controls cancer activation regul. protoc. Totowa, NJ: Humana Press; 2004, vol 2:301–11 pp.10.1385/1-59259-811-0:301Search in Google Scholar PubMed

15. Gajjar, S, Bora, V, Patel, BM. Repositioning of simvastatin for diabetic colon cancer: role of CDK4 inhibition and apoptosis. Mol Cell Biochem 2023;478:2337–49. https://doi.org/10.1007/s11010-023-04663-w.Search in Google Scholar PubMed

16. Huang, Y, Zhang, D, Xue, S, Wang, M, Cong, W. The potential of microalgae lipids for edible oil production. Appl Biochem Biotechnol 2016;180:438–51. https://doi.org/10.1007/s12010-016-2108-6.Search in Google Scholar PubMed

17. Mazurek, B, Ryszko, U, Kostrzewa, D, Chmiel, M, Kondracka, M. Brief characteristics of oxidative stability, fatty acids and metal content in selected berry seed extracts obtained by the SFE technique and used as potential source of nutrients. Food Chem 2022;367:130752. https://doi.org/10.1016/j.foodchem.2021.130752.Search in Google Scholar PubMed

18. Kamal, AM, Taha, MS, Mousa, AM. The radioprotective and anticancer effects of banana peels extract on male mice. J Food Nutr Res 2019;7:827–35. https://doi.org/10.12691/jfnr-7-12-3.Search in Google Scholar

19. Lillehoj, EP. Protein immunoblotting. In: Malik, VS, Lillehoj, EP, editors. Antibody techniques. Cambridge, United States: Academic Press; 1994:273–89 pp.10.1016/B978-0-12-466460-9.50016-XSearch in Google Scholar

20. Pound, JD. Immunochemical protocols, 2nd ed. Totowa, NJ: Humana Press; 1998:207–16 pp.10.1385/0896034933Search in Google Scholar

21. Saska, I, Gillon, AD, Hatsugai, N, Dietzgen, RG, Hara-Nishimura, I, Anderson, MA, et al.. An asparaginyl endopeptidase mediates in vivo protein backbone cyclization. J Biol Chem 2007;282:29721–8. https://doi.org/10.1074/jbc.M705185200.Search in Google Scholar PubMed

22. Laphanuwat, P, Jirawatnotai, S. Immunomodulatory roles of cell cycle regulators. Front Cell Dev Biol 2019;7:23. https://doi.org/10.3389/fcell.2019.00023.Search in Google Scholar PubMed PubMed Central

23. Oakes, V, Wang, W, Harrington, B, Lee, WJ, Beamish, H, Chia, KM, et al.. Cyclin A/Cdk2 regulates Cdh1 and claspin during late S/G2 phase of the cell cycle. Cell Cycle 2014;13:3302–11. https://doi.org/10.4161/15384101.2014.949111.Search in Google Scholar PubMed PubMed Central

24. Yang, TY, Chang, GC, Chen, KC, Hung, HW, Hsu, KH, Sheu, GT, et al.. Sustained activation of ERK and Cdk2/cyclin-A signaling pathway by pemetrexed leading to S-phase arrest and apoptosis in human non-small cell lung cancer A549 cells. Eur J Pharmacol 2011;663:17–26. https://doi.org/10.1016/j.ejphar.2011.04.057.Search in Google Scholar PubMed

25. De Azevedo, WF, Gaspar, RT, Canduri, F, Camera, JC, Da Silveira, NJF. Molecular model of cyclin-dependent kinase 5 complexed with roscovitine. Biochem Biophys Res Commun 2002;297:1154–8. https://doi.org/10.1016/S0006-291X(02)02352-5.Search in Google Scholar PubMed

26. Zeid, IM, Al Thobaitil, SA, El Hag, GA, Alghamdi, SA, Umar, A, Hamdi, OA. Phytochemical and GC-MS analysis of bioactive compounds from Balanites aegyptiaca. Acta Sci Pharmaceut Sci 2019;3:129–34. https://doi.org/10.31080/ASPS.2019.03.0352.Search in Google Scholar

27. Padmini, N, Rashiya, N, Sivakumar, N, Kannan, ND, Manjuladevi, R, Rajasekar, P, et al.. In-vitro and in-vivo efficacy of methyl oleate and palmitic acid against ESBL producing MDR Escherichia coli and Klebsiella pneumoniae. Microb Pathog 2020;148:104446. https://doi.org/10.1016/j.micpath.2020.104446.Search in Google Scholar PubMed

28. Baldi, A, De Luca, A, Esposito, V, Campioni, M, Spugnini, EP, Citro, G. Tumor suppressors and cell-cycle proteins in lung cancer. Pathol Res Int 2011;2011:605042. https://doi.org/10.4061/2011/605042.Search in Google Scholar PubMed PubMed Central

29. Malumbres, M, Barbacid, M. Cell cycle, CDKs and cancer: a changing paradigm. Nat Rev Cancer 2009;9:153–66. https://doi.org/10.1038/nrc2602.Search in Google Scholar PubMed

30. Li, Z, Zhang, Y, Zhou, Y, Wang, F, Yin, C, Ding, L, et al.. Tanshinone IIA suppresses the progression of lung adenocarcinoma through regulating CCNA2-CDK2 complex and AURKA/PLK1 pathway. Sci Rep 2021;11:23681. https://doi.org/10.1038/s41598-021-03166-2.Search in Google Scholar PubMed PubMed Central

31. Nath, R, Singha, S, Nath, D, Das, G, Patra, JK, Talukdar, AD. Phytochemicals from Allium tuberosum Rottler ex Spreng show potent inhibitory activity against B-Raf, EGFR, K-Ras, and PI3K of non-small cell lung cancer targets. Appl Sci 2022;12:11749. https://doi.org/10.3390/app122211749.Search in Google Scholar

32. Zhu, S, Jiao, W, Xu, Y, Hou, L, Li, H, Shao, J, et al.. Palmitic acid inhibits prostate cancer cell proliferation and metastasis by suppressing the PI3K/Akt pathway. Life Sci 2021;286:120046. https://doi.org/10.1016/j.lfs.2021.120046.Search in Google Scholar PubMed

33. Lu, X, Yu, H, Ma, Q, Shen, S, Das, UN. Linoleic acid suppresses colorectal cancer cell growth by inducing oxidant stress and mitochondrial dysfunction. Lipids Health Dis 2010;9:106. https://doi.org/10.1186/1476-511X-9-106.Search in Google Scholar PubMed PubMed Central

34. Yamagata, K, Uzu, E, Yoshigai, Y, Kato, C, Tagami, M. Oleic acid and oleoylethanolamide decrease interferon-γ-induced expression of PD-L1 and induce apoptosis in human lung carcinoma cells. Eur J Pharmacol 2021;903:174116. https://doi.org/10.1016/j.ejphar.2021.174116.Search in Google Scholar PubMed

35. Dutta, A, Panchali, T, Khatun, A, Jarapala, SR, Das, K, Ghosh, K, et al.. Apoptotic effect of linoelaidic acid isolated from marine tapra fish oil (Ophisthopterus tardoore) via ROS generation and caspase activation on apoptotic effect of linoelaidic acid isolated from marine tapra fish oil (Ophisthopterus tardoore) via ROS generation and caspase activation on MCF cell line. Sci Rep 2023;13. https://doi.org/10.21203/rs.3.rs-2415712/v1.Search in Google Scholar

36. Tshering, G, Pimtong, W, Plengsuriyakarn, T, Na-Bangchang, K. Anti-angiogenic effects of beta-eudesmol and atractylodin in developing zebrafish embryos. Comp Biochem Physiol C Toxicol Pharmacol 2021;243:108980. https://doi.org/10.1016/j.cbpc.2021.108980.Search in Google Scholar PubMed

37. Dar, MY, Shah, WA, Rather, MA, Qurishi, Y, Hamid, A, Qurishi, MA. Chemical composition, in-vitro cytotoxic and antioxidant activities of the essential oil and major constituents of Cymbopogon jawarancusa (Kashmir). Food Chem 2011;129:1606–11. https://doi.org/10.1016/j.foodchem.2011.06.016.Search in Google Scholar

38. Kim, HY, Kim, JH. Sesquiterpenoids isolated from the rhizomes of genus Atractylodes. Chem Biodivers 2022;19:e202200703. https://doi.org/10.1002/cbdv.202200703.Search in Google Scholar PubMed

39. El Gizawy, HA, El Zanaty, SA, El Ghaly, EM, Seif-Eldein, NA. Thevetia peruviana leaves, HPLC profile, isolation, and in-vitro cytotoxicity. RSC Adv 2023;13:12072–9. https://doi.org/10.1039/D3RA00588G.Search in Google Scholar

Supplementary Material

This article contains supplementary material (https://doi.org/10.1515/znc-2024-0059).

Received: 2024-03-13
Accepted: 2024-05-10
Published Online: 2024-05-24
Published in Print: 2024-09-25

© 2024 Walter de Gruyter GmbH, Berlin/Boston

Articles in the same Issue

  1. Frontmatter
  2. Review
  3. Navigating the landscape of theranostics in nuclear medicine: current practice and future prospects
  4. Research Articles
  5. Insecticidal effect of new synthesized chalcone derivatives on Caribbean fruit fly, Anastrepha suspensa
  6. Cymbopogon proximus phytochemicals induce S-phase arrest in A549 lung cancer cell lines via CDK2/cyclin A2 inhibition: gas chromatography-mass spectrometry and molecular docking analyses
  7. Chemical constituents from the Saposhnikovia divaricata and their antiproliferative activity
  8. Development and assessment of novel pyrazole–thiadiazol hybrid derivatives as VEGFR-2 inhibitors: design, synthesis, anticancer activity evaluation, molecular docking, and molecular dynamics simulation
  9. In vitro antibacterial and antioxidant activity of flavonoids from the roots of Tephrosia vogelii: a combined experimental and computational study
  10. Chemical composition and the anti-inflammatory effect of volatile compounds from Anaxagorea luzonensis A. Gray
https://doi.org/10.1515/znc-2024-0059
Keywords for this article
Cymbopogon proximus; halfabar; lung cancer; in silico study; western blot

Articles in the same Issue

  1. Frontmatter
  2. Review
  3. Navigating the landscape of theranostics in nuclear medicine: current practice and future prospects
  4. Research Articles
  5. Insecticidal effect of new synthesized chalcone derivatives on Caribbean fruit fly, Anastrepha suspensa
  6. Cymbopogon proximus phytochemicals induce S-phase arrest in A549 lung cancer cell lines via CDK2/cyclin A2 inhibition: gas chromatography-mass spectrometry and molecular docking analyses
  7. Chemical constituents from the Saposhnikovia divaricata and their antiproliferative activity
  8. Development and assessment of novel pyrazole–thiadiazol hybrid derivatives as VEGFR-2 inhibitors: design, synthesis, anticancer activity evaluation, molecular docking, and molecular dynamics simulation
  9. In vitro antibacterial and antioxidant activity of flavonoids from the roots of Tephrosia vogelii: a combined experimental and computational study
  10. Chemical composition and the anti-inflammatory effect of volatile compounds from Anaxagorea luzonensis A. Gray
Sign up now to receive a 20% welcome discount
Institutional Access
How does access work?
Have an idea on how to improve our website?
Please write us.
© 2025 De Gruyter Brill
Downloaded on 26.11.2025 from https://www.degruyterbrill.com/document/doi/10.1515/znc-2024-0059/pdf
Scroll to top button