Ranganathan Santhalakshmi, Halagowder Devaraj, Sivasithambaram Niranjali Devaraj
Department of Biochemistry, University of Madras, Guindy Campus, Chennai, India.
University Grants commission, New Delhi, India.
PLoS One. 2015 Oct 22;10(10):e0141370. doi: 10.1371/journal.pone.0141370. eCollection 2015.
Quercetin is a dietary flavonoid which exerts anti-oxidant, anti-inflammatory and anti-cancer properties. In this study, we investigated the anti-proliferative effect of quercetin in two breast cancer cell lines (MCF-7 and MDA-MB-231), which differed in hormone receptor. IC50 value (37μM) of quercetin showed significant cytotoxicity in MCF-7 cells, which was not observed in MDA-MB-231 cells even at 100μM of quercetin treatment. To study the response of cancer cells to quercetin, with respect to different hormone receptors, both the cell lines were treated with a fixed concentration (40μM) of quercetin. MCF-7 cells on quercetin treatment showed more apoptotic cells with G1 phase arrest. In addition, quercetin effectively suppressed the expression of CyclinD1, p21, Twist and phospho p38MAPK, which was not observed in MDA-MB-231 cells. To analyse the molecular mechanism of quercetin in exerting an apoptotic effect in MCF-7 cells, Twist was over-expressed and the molecular changes were observed after quercetin administration. Quercetin effectively regulated the expression of Twist, in turn p16 and p21 which induced apoptosis in MCF-7 cells. In conclusion, quercetin induces apoptosis in breast cancer cells through suppression of Twist via p38MAPK pathway.
槲皮素是一种膳食类黄酮,具有抗氧化、抗炎和抗癌特性。在本研究中,我们调查了槲皮素对两种激素受体不同的乳腺癌细胞系(MCF-7和MDA-MB-231)的抗增殖作用。槲皮素的IC50值(37μM)在MCF-7细胞中显示出显著的细胞毒性,即使在100μM槲皮素处理下,MDA-MB-231细胞中也未观察到这种毒性。为了研究癌细胞对槲皮素的反应,针对不同的激素受体,用固定浓度(40μM)的槲皮素处理这两种细胞系。槲皮素处理后的MCF-7细胞显示出更多处于G1期停滞的凋亡细胞。此外,槲皮素有效抑制了CyclinD1、p21、Twist和磷酸化p38MAPK的表达,而MDA-MB-231细胞中未观察到这种情况。为了分析槲皮素在MCF-7细胞中发挥凋亡作用的分子机制,使Twist过表达,并在给予槲皮素后观察分子变化。槲皮素有效调节了Twist的表达,进而调节了p16和p21的表达,从而诱导MCF-7细胞凋亡。总之,槲皮素通过p38MAPK途径抑制Twist来诱导乳腺癌细胞凋亡。