title: Resveratrol Induces Cancer Cell Apoptosis through MiR-326/PKM2-Mediated ER Stress and Mitochondrial Fission.
abstract: 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 IC50values 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.
authors.affiliation: Institute of Biotechnology, Key Laboratory of Chemical Biology and Molecular Engineering of National Ministry of Education, Shanxi University , Taiyuan 030006, China.
authors.forename: Haili
authors.initials: H
authors.lastname: Wu
authors.affiliation: Institute of Biotechnology, Key Laboratory of Chemical Biology and Molecular Engineering of National Ministry of Education, Shanxi University , Taiyuan 030006, China.
authors.forename: Yingying
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Institutes of Biomedical Sciences, Shanxi University , Taiyuan 030006, China.
authors.forename: Changxin
authors.initials: C
authors.lastname: Wu
authors.affiliation: Institute of Biotechnology, Key Laboratory of Chemical Biology and Molecular Engineering of National Ministry of Education, Shanxi University , Taiyuan 030006, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Yang
authors.affiliation: School of Life Science, Shanxi University , Taiyuan 030006, China.
authors.forename: Hanqing
authors.initials: H
authors.lastname: Li
authors.affiliation: Institute of Biotechnology, Key Laboratory of Chemical Biology and Molecular Engineering of National Ministry of Education, Shanxi University , Taiyuan 030006, China.|Institutes of Biomedical Sciences, Shanxi University , Taiyuan 030006, China.
authors.forename: Zhuoyu
authors.initials: Z
authors.lastname: Li
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008928:Mitochondria / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D063154:Mitochondrial Dynamics / Q000187:drug effects*; D009369:Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*; D013963:Thyroid Hormones / Q000235:genetics / Q000378:metabolism*; D000097810:Thyroid Hormone-Binding Proteins
chemical_list: D002352:Carrier Proteins; D008565:Membrane Proteins; D035683:MicroRNAs; D000077185:Resveratrol; D013267:Stilbenes; D013963:Thyroid Hormones; D000097810:Thyroid Hormone-Binding Proteins; C545322:MIRN326 microRNA, human
keywords: ER stress; PKM2; miR-326; mitochondrial fission; resveratrol