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

摘要

本研究调查了从非洲毛象中分离出的橙皮苷和木犀草素在人乳腺癌细胞系 (MCF-7)中抗癌活性的分子机制。使用 3-[4,5-二甲基噻唑-2-基]-2,5-二苯基溴化四唑 (MTT) 细胞毒性试验评估 MCF-7 细胞在橙皮苷和木犀草素处理后的活力；流式细胞仪分析细胞凋亡活性和对细胞周期进程的影响；对关键凋亡调控基因（caspase-3、-8、-9、Bcl-2和Bax ）表达的影响) 和凋亡 microRNA (-16、-21 和 -34a) 使用定量实时 PCR 进行评估。橙皮苷和木犀草素以剂量和时间依赖性方式降低细胞活力，导致凋亡细胞显着积累到 G0/G1 和亚 G1 细胞周期阶段，通过内在和外在途径诱导细胞凋亡，下调抗细胞凋亡、Bcl-2和上调的促凋亡蛋白 Bax。此外，橙皮苷和木犀草素显着下调 MCF-7 中 miR-21 的表达并上调 miR-16 和 -34a 的表达。Spearman 秩分析显示Bcl-2与 miR-21 呈正相关，Bcl- 2呈负相关，miR-16和-34a。这项研究的结果为乳腺癌细胞系中木犀草素和橙皮苷的抗癌活性的分子基础提供了新的证据。

由 Ramaswamy H. Sarma 传达