Myricetin Exerts its Apoptotic Effects on MCF-7 Breast Cancer Cells through Evoking the BRCA1-GADD45 Pathway

OBJECTIVE: Myricetin is a polyphenol flavonoid with nutraceutical values which is abundantly found as the main ingredient of various foods and beverages. It has been reported that the function of myricetin is to trigger apoptosis in several types of cancers. The present study intended to investigate the apoptotic effects of myricetin on MCF-7 breast cancer cells and to assess its possible mechanisms of action. MATERIALS AND METHODS: MCF-7 breast cancer cells were assigned to four groups: Control (cells in normal condition); myricetin (cells treated with the IC50 dosage of myricetin) in three different incubation times (24, 48, and 72 h). The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, annexin V assay, flow cytometry, real-time polymerase chain reaction (PCR), and caspase-3 assay were used to estimate the apoptosis function of myricetin in breast cancer. RESULTS: The expression levels of apoptosis-related genes caspase-3, caspase-8, caspase-9, and the BAX /Bcl-2 ratio as well as the expression of p53, BRCA1, GADD45 genes were significantly increased following the treatment of MCF-7 breast cancer cells with myricetin. The annexin V assay demonstrated the significant expression of annexin which was also detected by flow cytometry. CONCLUSION: Myricetin efficiently induces apoptosis in MCF-7 breast cancer cells by evoking both extrinsic and intrinsic apoptotic pathways. Myricetin may exert its apoptotic effects on MCF-7 cells by inducing the BRCA1- GADD45 pathway.