Anti-cancer Effect of Apigenin on Human Breast Carcinoma MDA-MB-231 through Cell Cycle Arrest and Apoptosis
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Apigenin, a common natural product that is found in many plants and vegetables, has been reported to have many biological activities, including antioxidative, anti-inflammatory, and anticancer effects. The triple- negative breast carcinoma cell line MDA-MB-231 is known to be highly invasive and resistant to chemotherapy. In this study, we investigated the anticancer effect of apigenin on human MDA-MB-231 cells. First, the cytotoxicity of apigenin toward MDA-MB-231 cells was analyzed by MTT assay. Then, the cell cycle and apoptotic effects of apigenin were examined, and the molecular mechanism underlying its anticancer activity was explored. Apigenin inhibited the growth of the cells in a dose-dependent manner, correlating with the cell cycle arrest at the G2-M phase as well as an increase of early apoptosis. The cell-cycle inhibitory effect was highly associated with the increased expression of p21 and decreased expression of CDK6, cyclin D1, and cyclin B1. The induction of apoptosis by apigenin was associated with the upregulated expression of cleaved PARP and cleaved caspase-3, -7, and -9.
Abstract
Apigenin, a common natural product that is found in many plants and vegetables, has been reported to have many biological activities, including antioxidative, anti-inflammatory, and anticancer effects. The triple- negative breast carcinoma cell line MDA-MB-231 is known to be highly invasive and resistant to chemotherapy. In this study, we investigated the anticancer effect of apigenin on human MDA-MB-231 cells. First, the cytotoxicity of apigenin toward MDA-MB-231 cells was analyzed by MTT assay. Then, the cell cycle and apoptotic effects of apigenin were examined, and the molecular mechanism underlying its anticancer activity was explored. Apigenin inhibited the growth of the cells in a dose-dependent manner, correlating with the cell cycle arrest at the G2-M phase as well as an increase of early apoptosis. The cell-cycle inhibitory effect was highly associated with the increased expression of p21 and decreased expression of CDK6, cyclin D1, and cyclin B1. The induction of apoptosis by apigenin was associated with the upregulated expression of cleaved PARP and cleaved caspase-3, -7, and -9.
참고문헌 (36)
- Sorlie T, "Gene expression profiles do not consistently predict the clinical treatment response in locally advanced breast cancer", Mol. Cancer Ther, 5, pp.2914~2918 (2006)
- van de Vijver MJ, "A gene-expression signature as a predictor of survival in breast cancer", N. Engl. J. Med, 347, pp.1999~2009 (2009)
- Hudis CA, "Triple-negative breast cancer: an unmet medical need", Oncologist, 16(Suppl 1), pp.1~11 (2011)
- Dent R, "Triple-negative breast cancer: clinical features and patterns of recurrence", Clin. Cancer Res, 13, pp.4429~4434 (2007)
- Papay ZE, "Study on the pulmonary delivery system of apigeninloaded albumin nanocarriers with antioxidant activity", J. Aerosol. Med. Pulm. Drug Deliv, 30, pp.274~288 (2017)
- Wang YC, "In vitro anti-inflammatory effect of apigenin in the Helicobacter pylori-infected gastric adenocarcinoma cells", Food Chem. Toxicol, 53, pp.376~383 (2013)
- Yan X, "Apigenin in cancer therapy: anti-cancer effects and mechanisms of action", Cell Biosci, 7, pp.50~ (2017)
- Ozcelik B, "Cytotoxicity, antiviral and antimicrobial activities of alkaloids, flavonoids, and phenolic acids", Pharm. Biol, 49, pp.396~402 (2011)
- Zhang W, "Apigenin inhibits enterovirus-71 infection by disrupting viral RNA association with trans-acting factors", PLoS One, 9, pp.e110429~ (2014)
- Birt DF, "Anti-mutagenesis and anti-promotion by apigenin, robinetin and indole-3-carbinol", Carcinogenesis, 7, pp.959~963 (1986)
- Huang C, "Chrysin, abundant in morinda citrifolia fruit water-EtOAc extracts, combined with apigenin synergistically induced apoptosis and inhibited migration in human breast and liver cancer cells", J. Agric. Food Chem, 64, pp.4235~4245 (2016)
- Lee YM, "Inhibition of glutamine utilization sensitizes lung cancer cells to apigenin- induced apoptosis resulting from metabolic and oxidative stress", Int. J. Oncol, 48, pp.399~408 (2016)
- Gupta S, "Involvement of nuclear factorkappa B, Bax and Bcl-2 in induction of cell cycle arrest and apoptosis by apigenin in human prostate carcinoma cells", Oncogene, 21, pp.3727~3738 (2002)
- Angulo P, "Natural compounds targeting major cell signaling pathways: a novel paradigm for osteosarcoma therapy", J. Hematol. Oncol, 10, pp.10~ (2017)
- Zhao G, "Apigenin inhibits proliferation and invasion, and induces apoptosis and cell cycle arrest in human melanoma cells", Oncol. Rep, 37, pp.2277~2285 (2017)
- Cardenas H, "Dietary apigenin exerts immune-regulatory activity in vivo by reducing NF-κB activity, halting leukocyte infiltration and restoring normal metabolic function", Int. J. Mol. Sci, 17, pp.323~ (2016)
- Nelson N, "Apigenin: selective CK2 inhibitor increases Ikaros expression and improves T cell homeostasis and function in murine pancreatic cancer", PLoS One, 12, pp.e0170197~ (2017)
- Lakin ND, "Regulation of p53 in response to DNA damage", Oncogene, 18, pp.7644~7655 (1999)
- Ballestar E, "Epigenetic gene regulation in cancer", Adv. Genet, 61, pp.247~267 (2008)
- Koh DW, "Mediation of cell death by poly(ADP-ribose) polymerase-1", Pharmacol. Res, 52, pp.5~14 (2005)
- Matt S, "The DNA damage-induced cell death response: a roadmap to kill cancer cells", Cell Mol. Life Sci, 73, pp.2829~2850 (2016)
- Vrhovac Madunic I, "Apigenin, a dietary flavonoid, induces apoptosis, DNA damage, and oxidative stress in human breast cancer MCF-7 and MDA MB-231 cells", Naunyn. Schmiedebergs Arch. Pharmacol, 391, pp.537~550 (2018)
- Tseng TH, "Inhibition of MDA-MB-231 breast cancer cell proliferation and tumor growth by apigenin through induction of G2", M arrest and histone H3 acetylation-mediated p21(WAF1, Environ. Toxicol, pp.2017, 32[DOI]
- Li Z, "Evaluation of CCND1 amplification and CyclinD1 expression: diffuse and strong staining of CyclinD1 could have same predictive roles as CCND1 amplification in ER positive breast cancers", Am. J. Transl. Res, 8, pp.142~153 (2016)
- Liu L, "High expression of Ras-related protein 1A promotes an aggressive phenotype in colorectal cancer via PTEN", FOXO3, J. Exp. Clin. Cancer Res, pp.2018, 37[DOI]
- Andisheh-Tadbir A, "Expression of CDK6 in oral squamous cell carcinomas", Asian Pac. J. Cancer Prev, 19, pp.1013~1016 (2012)
- Li B, "Knockdown of CDK6 enhances glioma sensitivity to chemotherapy", Oncol. Rep, 28, pp.909~914 (2012)
- Wang Z, "Cyclin B1", Cdk1 coordinates mitochondrial respiration for cellcycle G2, Dev. Cell, pp.2014, 29[DOI]
- Zhou L, "The prognostic value of Cyclin B1 in pancreatic cancer", Med. Oncol, 31, pp.107~ (2014)
- Fang Y, "Cyclin b1 suppresses colorectal cancer invasion and metastasis by regulating E-cadherin", PLoS One, 10, pp.e0126875~ (2015)
- Kabala-Dzik A, "Flavonoids, bioactive components of propolis, exhibit cytotoxic activity and induce cell cycle arrest and apoptosis in human breast cancer cells MDA-MB-231 and MCF-7 - a comparative study", Cell Mol. Biol. (Noisy-le-grand), 64, pp.1~10 (2018)
- Yang J, "Inhibition of PI3K", Akt, Biomed. Pharmacother, pp.2018, 103[DOI]
- Maeda Y, "Apigenin induces apoptosis by suppressing Bcl-xl and Mcl- 1 simultaneously via signal transducer and activator of transcription 3 signaling in colon cancer", Int. J. Oncol, pp.4308~ (2018)[DOI]
- Chen D, "Inhibition of proteasome activity by the dietary flavonoid apigenin is associated with growth inhibition in cultured breast cancer cells and xenografts", Breast Cancer Res, 9, pp.R80~ (2007)
- Ding J, "Wogonin and related natural flavones overcome tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) protein resistance of tumors by down-regulation of c-FLIP protein and up-regulation of TRAIL receptor 2 expression", J. Biol. Chem, 287, pp.641~649 (2012)
- Cao X, "Autophagy inhibition enhances apigenin-induced apoptosis in human breast cancer cells", Chin. J. Cancer Res, 25, pp.212~222 (2013)