Toxicarioside O induces protective autophagy in a sirtuin-1-dependent manner in colorectal cancer cells

文献类型： 外文期刊

第一作者： Huang, Yong-Hao

作者： Huang, Yong-Hao;Sun, Yan;Huang, Feng-Ying;Li, Yue-Nan;Wang, Cai-Chun;Tan, Guang-Hong;Huang, Canhua;Huang, Yong-Hao;Sun, Yan;Huang, Feng-Ying;Li, Yue-Nan;Wang, Cai-Chun;Tan, Guang-Hong;Huang, Canhua;Mei, Wen-Li;Dai, Hao-Fu;Huang, Canhua;Huang, Canhua

作者机构：

关键词： colorectal cancer;toxicarioside O (TCO);autophagy;apoptosis;sirtuin-1 (SIRT1)

期刊名称：ONCOTARGET （ 影响因子：5.168； 五年影响因子：5.312 ）

ISSN： 1949-2553

年卷期： 2017 年 8 卷 32 期

页码：

收录情况： SCI

摘要： Colorectal cancer is the most common cancer. It has high morbidity and mortality worldwide, and more effective treatment strategies need to be developed. Toxicarioside O (TCO), a natural product derived from Antiaris toxicaria, has been shown to be a potential anticancer agent. However, the molecular mechanisms involved remain poorly understood. In this study, our results demonstrated that TCO can induce both apoptosis and autophagy in colorectal cancer cells. Moreover, TCO-induced autophagy was due to the increase of the expression and activity of the enzyme sirtuin-1 (SIRT1), and subsequent inhibition of the Akt/mTOR pathway. Inhibition of SIRT1 activity by its inhibitor, EX-527, attenuated TCO-induced autophagy. Of interest, inhibition of autophagy by chloroguine, an autophagy inhibitor, enhanced TCO-induced apoptotic cell death, suggesting that autophagy plays a protective role in TCO-induced apoptosis. Together, these findings suggest that combination of TCO and autophagy inhibitor may be a novel strategy suitable for potentiating the anticancer activity of TCO for treatment of colorectal cancer.

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