Dioscin inhibits colon cancer cells’ growth by reactive oxygen species-mediated mitochondrial dysfunction and p38 and JNK pathways

Dioscin is a natural steroid saponin derived from several plants that shows potent anticancer effects against a variety of cancer cells. Here, we investigated the antitumor effect of dioscin against human colon cancer cells and evaluated the molecular mechanism involved in this process. The cell cytotoxicity was studied by the MTT assay and BrdU incorporation. The proapoptotic mechanism of dioscin was characterized by flow cytometry analysis. A western blot and an immunofluorescence staining were used to investigate how dioscin induces apoptosis in vitro. In our study, dioscin could significantly inhibit the growth of colon cancer cells in a time-dependent and dose-dependent manner. Dioscin induces apoptosis and reactive oxygen species (ROS) generation, promoting the disruption of mitochondrial membrane potential, Bax translocation to the mitochondria, cytochrome C release to cytosol, activations of caspase-9/3, PARP cleavage, and subsequent apoptosis. Dioscin-induced apoptosis was accompanied by sustained phosphorylation of JNK, p38-MAPK. N-acetyl-L-cysteine, a scavenger of ROS, significantly reversed dioscin-induced cell death and activation of JNK and p38. Collectively, the data indicate that the induction of apoptosis by dioscin is mediated through ROS proteins, which are critical upstream signals for JNK/p38-MAPK activation. *Shu Li and Binbin Cheng contributed equally to the writing of this article. Correspondence to Shuang Li, MSc, Department of Gastroenterology, Baoshan Branch, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 201900, China Tel:+86 215 660 1100 x317 fax: +86 218 187 1559; e-mail: lishuangbs@126.com Received August 28, 2017 Accepted December 9, 2017 Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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