Open AccessToxicarioside O induces protective autophagy in a sirtuin-1-dependent manner in colorectal cancer cells
Author(s) -
Yonghao Huang,
Yan Sun,
FengYing Huang,
Yue-Nan Li,
Cai-Chun Wang,
WenLi Mei,
HaoFu Dai,
Guangming Tan,
Canhua Huang
Publication year - 2017
Publication title -
oncotarget
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.373
H-Index - 127
ISSN - 1949-2553
DOI - 10.18632/oncotarget.17189
Subject(s) - autophagy , sirtuin , colorectal cancer , medicine , cancer research , cancer , sirtuin 1 , biology , downregulation and upregulation , apoptosis , gene , genetics , acetylation
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.