Anti-migratory effect of curcumin on A-549 lung cancer cells via epigenetic reprogramming of RECK/ matrix metalloproteinase axis
Abstract
Objectives
The aim of this study was to investigate the effects of curcumin on the viability, migration, and apoptosis of A549 lung cancer cells. Furthermore, RECK/MMPs axis as a probable regulator of cancer cell migration was assessed.
Methods
In this study, effect of curcumin on viability changes, cell migration, and percentage of apoptosis of A549 non-small cell lung carcinoma was examined. The methylation status of RECK gene was investigated using MS-HRM technique. Moreover, expression changes of genes involved in apoptosis and migration (including CASP3, CASP8, CASP9, BAX, BCL2, MMP9, MMP2, and RECK) were investigated by quantitative Real-Time PCR.
Results
The results of MTT assay showed that the cytotoxic effect of curcumin was in a dose dependent manner. Flow cytometry results demonstrated a significant increase in the percentage of apoptotic cells in curcumin treated group. In addition, curcumin inhibited migration rate in lung cancer cells. qRT-PCR revealed that expression of the candidate genes was in line with suppressed growth and migration. This could be due to, decreased methylation of the RECK gene promoter after curcumin treatment.
Conclusions
Curcumin inhibited lung cancer cells through various molecular pathways. RECK/MMPs axis as a regulator of cancer cell migration was modulated after curcumin treatment and invasion of lung cancer cells was decreased.
-
Research funding: Not applicable.
-
Author contributions: Conceived and designed the experiments: SM and DS; Performed the experiments: SM and MA; Statistical analysis: SAR; Wrote the paper: SM and DS. All authors read and approved the final manuscript.
-
Competing interests: The author declares that there is no conflict of interest.
-
Informed consent: Not applicable.
-
Ethical approval: Not applicable.
-
Data availability: The data sets used and analyzed during the current study are available from the corresponding author on reasonable request.
References
1. Kwon, SB, Kim, MJ, Sun Young, H, Park, GW, Choi, KD, Jung, SH, et al.. H9 induces apoptosis via the intrinsic pathway in non-small-cell lung cancer A549 cells. J Microbiol Biotechnol 2015;25:343–52. https://doi.org/10.4014/jmb.1412.12074.Suche in Google Scholar PubMed
2. Kogita, A, Togashi, Y, Hayashi, H, SOGAbE, SH, Terashima, M, De Velasco, MA, et al.. Hypoxia induces resistance to ALK inhibitors in the H3122 non-small cell lung cancer cell line with an ALK rearrangement via epithelial-mesenchymal transition. Int J Oncol 2014;45:1430–6. https://doi.org/10.3892/ijo.2014.2574.Suche in Google Scholar PubMed PubMed Central
3. Firouzi Amoodizaj, F, Baghaeifar, S, Taheri, E, Farhoudi SefidanJadid, M, Safi, M, Seyyed Sani, N, et al.. Enhanced anticancer potency of doxorubicin in combination with curcumin in gastric adenocarcinoma. J Biochem Mol Toxicol 2020;34:22486. https://doi.org/10.1002/jbt.22486.Suche in Google Scholar PubMed
4. Taheri, E, Ghorbani, S, Safi, M, Sani, NS, Amoodizaj, FF, Heidari, M, et al.. Inhibition of colorectal cancer cell line CaCo-2 by essential oil of Eucalyptus camaldulensis through induction of apoptosis. Acta Med Iran 2020;58:260–5. https://doi.org/10.18502/acta.v58i6.4051.Suche in Google Scholar
5. Wang, TY, Chen, JX. Effects of curcumin on vessel formation insight into the pro-and antiangiogenesis of curcumin. Evid Based Complementary Altern Med 2019;2019:1390795. https://doi.org/10.1155/2019/1390795.Suche in Google Scholar PubMed PubMed Central
6. Jadid, MF, Shademan, B, Chavoshi, R, Seyyedsani, N, Aghaei, E, Taheri, E, et al.. Enhanced anticancer potency of hydroxytyrosol and curcumin by PLGA-PAA nano-encapsulation on PANC-1 pancreatic cancer cell line. Environ Toxicol 2021;36:1043–51.10.1002/tox.23103Suche in Google Scholar PubMed
7. Anand, P, Sundaram, C, Jhurani, S, Kunnumakkara, AB, Aggarwal, BB. Curcumin and cancer: an “old-age” disease with an “age-old” solution. Cancer Lett 2008;267:133–64. https://doi.org/10.1016/j.canlet.2008.03.025.Suche in Google Scholar PubMed
8. Jin, H, Qiao, F, Wang, Y, Xu, Y, Shang, Y. Curcumin inhibits cell proliferation and induces apoptosis of human non-small cell lung cancer cells through the upregulation of miR-192-5p and suppression of PI3K/Akt signaling pathway. Oncol Rep 2015;34:2782–9. https://doi.org/10.3892/or.2015.4258.Suche in Google Scholar PubMed
9. Li, X, Lu, H, Fan, G, He, M, Sun, Y, Xu, K, et al.. A novel interplay between HOTAIR and DNA methylation in osteosarcoma cells indicates a new therapeutic strategy. J Cancer Res Clin Oncol 2017;143:2189–200. https://doi.org/10.1007/s00432-017-2478-3.Suche in Google Scholar PubMed
10. Jeon, HW, Lee, KJ, Lee, SH, Kim, WH, Lee, YM. Attenuated expression and function of the RECK tumor suppressor under hypoxic conditions is mediated by the MAPK signaling pathways. Arch Pharm Res (Seoul) 2011;34:137–45. https://doi.org/10.1007/s12272-011-0116-1.Suche in Google Scholar PubMed
11. Alexius-Lindgren, M, Andersson, E, Lindstedt, I, Engström, W. The RECK gene and biological malignancy–its significance in angiogenesis and inhibition of matrix metalloproteinases. Anticancer Res 2014;34:3867–73.Suche in Google Scholar
12. Jabłońska-Trypuć, A, Matejczyk, M, Rosochacki, S. Matrix metalloproteinases (MMPs), the main extracellular matrix (ECM) enzymes in collagen degradation, as a target for anticancer drugs. J Enzym Inhib Med Chem 2016;31:177–83. https://doi.org/10.3109/14756366.2016.1161620.Suche in Google Scholar PubMed
13. Zhang, C, Ling, Y, Zhang, C, Xu, Y, Gao, L, Li, R, et al.. The silencing of RECK gene is associated with promoter hypermethylation and poor survival in hepatocellular carcinoma. Int J Biol Sci 2012;8:451. https://doi.org/10.7150/ijbs.4038.Suche in Google Scholar PubMed PubMed Central
14. Lu, Y, Zabihula, B, Yibulayin, W, Liu, X. Methylation and expression of RECK, P53 and RUNX genes in patients with esophageal cancer. Oncol Lett 2017;14:5293–8. https://doi.org/10.3892/ol.2017.6863.Suche in Google Scholar PubMed PubMed Central
15. Tveden‐Nyborg, P, Bergmann, TK, Jessen, N, Simonsen, U, Lykkesfeldt, J. BCPT policy for experimental and clinical studies. Basic Clin Pharmacol Toxicol 2021;128:4–8. https://doi.org/10.1111/bcpt.13492.Suche in Google Scholar PubMed
16. Mahdavi, S, Kheyrollahi, M, Sheikhloei, H, Isazadeh, A. Antibacterial and antioxidant activities of essential oil on food borne bacteria. Open Microbiol J 2019;13:81–5. https://doi.org/10.2174/1874285801913010081.Suche in Google Scholar
17. Hajazimian, S, Maleki, M, Mehrabad, SD, Isazadeh, A. Human Wharton’s jelly stem cells inhibit endometriosis through apoptosis induction. Reproduction 2020;159:549–58. https://doi.org/10.1530/rep-19-0597.Suche in Google Scholar PubMed
18. Jadid, MF, Aghaei, E, Taheri, E, Seyyedsani, N, Chavoshi, R, Abbasi, S, et al.. Melatonin increases the anticancer potential of doxorubicin in caco-2 colorectal cancer cells. Environ Toxicol 2021;36:1061–9.10.1002/tox.23105Suche in Google Scholar PubMed
19. Maroufi, NF, Vahedian, V, Hemati, S, Rashidi, MR, Akbarzadeh, M, Zahedi, M, et al.. Targeting cancer stem cells by melatonin: effective therapy for cancer treatment. Pathol Res Pract 2020;216:152919. https://doi.org/10.1016/j.prp.2020.152919.Suche in Google Scholar PubMed
20. Yang, H, Huang, S, Wei, Y, Cao, S, Pi, C, Feng, T, et al.. Curcumin enhances the anticancer effect of 5-fluorouracil against gastric cancer through down-regulation of COX-2 and NF-κB signaling pathways. J Cancer 2017;8:3697. https://doi.org/10.7150/jca.20196.Suche in Google Scholar PubMed PubMed Central
21. Akkoç, Y, Berrak, Ö, Arısan, ED, Obakan, P, Çoker-Gürkan, A, Palavan-Ünsal, N. Inhibition of PI3K signaling triggered apoptotic potential of curcumin which is hindered by Bcl-2 through activation of autophagy in MCF-7 cells. Biomed Pharmacother 2015;71:161–71. https://doi.org/10.1016/j.biopha.2015.02.029.Suche in Google Scholar PubMed
22. Toteda, G, Lupinacci, S, Vizza, D, Bonofiglio, R, Perri, E, Bonofiglio, M, et al.. High doses of hydroxytyrosol induce apoptosis in papillary and follicular thyroid cancer cells. J Endocrinol Invest 2017;40:153–62. https://doi.org/10.1007/s40618-016-0537-2.Suche in Google Scholar PubMed
23. Oh, J, Takahashi, R, Kondo, S, Mizoguchi, A, Adachi, E, Sasahara, RM, et al.. The membrane-anchored MMP inhibitor RECK is a key regulator of extracellular matrix integrity and angiogenesis. Cell 2001;107:789–800. https://doi.org/10.1016/s0092-8674(01)00597-9.Suche in Google Scholar PubMed
24. Jia, W, Deng, F, Fu, W, Hu, J, Chen, G, Gao, X, et al.. Curcumin suppresses wilms’ tumor metastasis by inhibiting RECK methylation. Biomed Pharmacother 2019;111:1204–12. https://doi.org/10.1016/j.biopha.2018.12.111.Suche in Google Scholar PubMed
25. Zhang, C, Jiang, M, Zhou, N, Hou, H, Li, T, Yu, H, et al.. Use tumor suppressor genes as biomarkers for diagnosis of non-small cell lung cancer. Sci Rep 2021;11:1–3. https://doi.org/10.1038/s41598-020-80735-x.Suche in Google Scholar PubMed PubMed Central
© 2022 Walter de Gruyter GmbH, Berlin/Boston
Artikel in diesem Heft
- Frontmatter
- Letter to the Editor
- COVID-19 pandemic: transmission of SARS-CoV-2 in animals, a risk for human beings
- Original Articles
- Anti Mullerian hormone as a diagnostic tool for polycystic ovary syndrome in women of reproductive age with morbid obesity
- Potential tumor marker for hepatocellular carcinoma identification: PI3K and pro-inflammatory cytokines (TGF-β, IL-1, and IL-6)
- The investigation of the frequency of the alpha-1-antitrypsin phenotype in patients with liver cirrhosis
- Anti-oxidant effect of metformin through AMPK/SIRT1/PGC-1α/SIRT3– independent GPx1 expression in the heart of mice with endometriosis
- Hypoxia-inducible factor-1α and ischemia-modified albumin levels in intensive care COVID-19 Patients
- Association between TP53 Arg72Pro variant and recurrent pregnancy loss in the Greek population
- Selective estrogen receptor α and β antagonist aggravate cardiovascular dysfunction in type 2 diabetic ovariectomized female rats
- Adrenocorticotropic hormone (ACTH) level and adrenal deficiency in patients with mucocutaneous pemphigus
- The effect of resistance training on serum levels of sex hormones and sperm quality in male rats under X-ray radiation
- The effect of high-intensity interval training on serum and adipose tissues vaspin levels in rats fed a high-fat high-sucrose diet
- Anti-migratory effect of curcumin on A-549 lung cancer cells via epigenetic reprogramming of RECK/ matrix metalloproteinase axis
- Efficacy of rectal progesterone on maternal and neonatal outcomes in pregnant women with Preterm Premature Rupture of membranes: a triple-blind randomised clinical trial
- Case Report
- Ovarian tissue cryopreservation in Malaysia: a case series
- Review Articles
- An overview of prognostic value of neurologic and cardiac biomarkers in patients with COVID-19 sequelae
- Potential role of melatonin in prevention and treatment of lung cancer
- Esketamine–A quick-acting novel antidepressant without the disadvantages of ketamine
Artikel in diesem Heft
- Frontmatter
- Letter to the Editor
- COVID-19 pandemic: transmission of SARS-CoV-2 in animals, a risk for human beings
- Original Articles
- Anti Mullerian hormone as a diagnostic tool for polycystic ovary syndrome in women of reproductive age with morbid obesity
- Potential tumor marker for hepatocellular carcinoma identification: PI3K and pro-inflammatory cytokines (TGF-β, IL-1, and IL-6)
- The investigation of the frequency of the alpha-1-antitrypsin phenotype in patients with liver cirrhosis
- Anti-oxidant effect of metformin through AMPK/SIRT1/PGC-1α/SIRT3– independent GPx1 expression in the heart of mice with endometriosis
- Hypoxia-inducible factor-1α and ischemia-modified albumin levels in intensive care COVID-19 Patients
- Association between TP53 Arg72Pro variant and recurrent pregnancy loss in the Greek population
- Selective estrogen receptor α and β antagonist aggravate cardiovascular dysfunction in type 2 diabetic ovariectomized female rats
- Adrenocorticotropic hormone (ACTH) level and adrenal deficiency in patients with mucocutaneous pemphigus
- The effect of resistance training on serum levels of sex hormones and sperm quality in male rats under X-ray radiation
- The effect of high-intensity interval training on serum and adipose tissues vaspin levels in rats fed a high-fat high-sucrose diet
- Anti-migratory effect of curcumin on A-549 lung cancer cells via epigenetic reprogramming of RECK/ matrix metalloproteinase axis
- Efficacy of rectal progesterone on maternal and neonatal outcomes in pregnant women with Preterm Premature Rupture of membranes: a triple-blind randomised clinical trial
- Case Report
- Ovarian tissue cryopreservation in Malaysia: a case series
- Review Articles
- An overview of prognostic value of neurologic and cardiac biomarkers in patients with COVID-19 sequelae
- Potential role of melatonin in prevention and treatment of lung cancer
- Esketamine–A quick-acting novel antidepressant without the disadvantages of ketamine