The effect of hesperidin and luteolin isolated from Eriocephalus africanus on apoptosis, cell cycle and miRNA expression in MCF-7

Abstract

This study investigates the molecular mechanisms underlying the anticancer activity of hesperidin and luteolin, isolated from Eriocephalus africanus, in the human breast carcinoma cell line (MCF-7). The viability of MCF-7 cells, upon treatment with hesperidin and luteolin, was evaluated using the 3-[4,5-dimethylthiazole-2-yl]-2,5-diphenyltetrazolium bromide (MTT) cytotoxicity assay; apoptotic activity and effect on cell cycle progression were analysed by flow cytometry; effect on expression of key apoptotic regulatory genes (caspase-3, -8, -9, Bcl-2 and Bax) and apoptotic microRNAs (-16, -21 and -34a) were evaluated using quantitative real-time PCR. Hesperidin and luteolin reduced cell viability in a dose and time-dependent manner, caused a significant accumulation of apoptotic cells into the G0/G1 and sub-G1 cell cycle phases, induced apoptosis through the intrinsic and extrinsic pathways, down-regulated anti-apoptotic, Bcl-2, and upregulated pro-apoptotic, Bax. In addition, hesperidin and luteolin significantly downregulated the expression of miR-21 and upregulated that of miR-16 and -34a in MCF-7. Spearman`s rank analysis revealed a positive correlation between Bcl-2 and miR-21 and negative correlation between Bcl-2, miR-16 and -34a. Findings from this study provide new evidence on the molecular basis of the anticancer activity of luteolin and hesperidin in breast cancer cell lines. Communicated by Ramaswamy H. Sarma