巴基斯坦卢比
细胞凋亡
白藜芦醇
赫拉
活力测定
化学
细胞
线粒体分裂
细胞生长
细胞生物学
生物
丙酮酸激酶
癌症研究
生物化学
糖酵解
新陈代谢
作者
Haili Wu,Yingying Wang,Changxin Wu,Peng Yang,Hanqing Li,Zhuoyu Li
标识
DOI:10.1021/acs.jafc.6b04549
摘要
Resveratrol (Res), a natural phytoalexin found in a variety of plants, has significant antitumor activity. Pyruvate kinase M2 (PKM2) has abnormally high expression in various tumor cells, and it has been implicated in the survival of tumors. However, whether and how Res inhibits PKM2 expression is poorly understood. In the present study, we found that treatment with Res inhibited cell proliferation and induced cell apoptosis. The IC50 values of Res against DLD1, HeLa, and MCF-7 cells were 75 ± 4.54, 50 ± 3.65, and 50 ± 3.32 μM, respectively. To elucidate mechanisms underlying its antitumor activities, serial experiments were performed. Results showed that reduction of PKM2 expression in tumor cells by Res treatment increased the expression of ER stress and mitochondrial fission proteins but reduced cell viability and the levels of fusion proteins. These phenomena were reversed by artificial overexpression of PKM2. Quantitative analyses showed that the expression of microRNA-326 (miR-326) was increased upon Res treatment. Treatment with the miR-326 mimic reduced PKM2 expression, promoting recovery from ER stress and mitochondrial fission. Overall, these results demonstrate that miR-326/PKM2-mediated ER stress and mitochondrial dysfunction participate in apoptosis induced by Res. These results provide novel insight into the molecular mechanisms by which Res suppresses tumors and further support for the use of Res as an antitumor drug.
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