Toxicarioside O induces protective autophagy in a sirtuin-1-dependent manner in colorectal cancer cells
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Yong-Hao Huang1,*, Yan Sun1,*, Feng-Ying Huang1,*, Yue-Nan Li1, Cai-Chun Wang1, Wen-Li Mei2, Hao-Fu Dai2, Guang-Hong Tan1 and Canhua Huang1,3
1Key Laboratory of Tropical Diseases and Translational Medicine of the Ministry of Education & Hainan Provincial Key Laboratory of Tropical Medicine, Hainan Medical College, Haikou 571199, China
2Institute of Tropical Bioscience and Biotechnology, Chinese Academy of Tropical Agricultural Sciences, Haikou 571199, China
3State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu 610041, China
*These authors have contributed equally to the work
Canhua Huang, email: firstname.lastname@example.org
Guang-Hong Tan, email: email@example.com
Hao-Fu Dai, email: firstname.lastname@example.org
Keywords: colorectal cancer, toxicarioside O (TCO), autophagy, apoptosis, sirtuin-1 (SIRT1)
Received: February 15, 2017 Accepted: March 21, 2017 Published: April 18, 2017
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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