Oncotarget

Research Papers:

Salvianolic acid B, a novel autophagy inducer, exerts antitumor activity as a single agent in colorectal cancer cells

Zhao Jing, Weiqiang Fei, Jichun Zhou, Lumin Zhang, Liuxi Chen, Xiaomin Zhang, Xiao Liang, Jiansheng Xie, Yong Fang, Xinbing Sui _, Weidong Han and Hongming Pan

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Oncotarget. 2016; 7:61509-61519. https://doi.org/10.18632/oncotarget.11385

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Abstract

Zhao Jing1,2,*, Weiqiang Fei2,*, Jichun Zhou3,*, Lumin Zhang2, Liuxi Chen1, Xiaomin Zhang1, Xiao Liang4, Jiansheng Xie2, Yong Fang1,2, Xinbing Sui1,2, Weidong Han1,2, Hongming Pan1,2

1Department of Medical Oncology, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China

2Biomedical Research Center and Key Laboratory of Biotherapy of Zhejiang Province, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China

3Department of Surgical Oncology, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China

4Department of General Surgery, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China

*These authors contributed equally to this work

Correspondence to:

Xinbing Sui, email: [email protected]

Weidong Han, email: [email protected]

Hongming Pan, email: [email protected]

Keywords: salvianolic acid B, natural compound, autophagy, cell death, colorectal cancer

Received: April 25, 2016     Accepted: August 13, 2016     Published: August 19, 2016

ABSTRACT

Salvianolic Acid B (Sal B), an active compound extracted from the Chinese herb Salvia miltiorrhiza, is attracting more and more attention due to its biological activities, including antioxidant, anticoagulant and antitumor effects. However, autophagy induction in cancer cells by Sal B has never been recognized. In this study, we demonstrated that Sal B induced cell death and triggered autophagy in HCT116 and HT29 cells in a dose-dependent manner. Specific inhibition of autophagy by 3-MA or shRNA targeting Atg5 rescued Sal B-induced cell death in vitro and in vivo, suggesting that Sal B-induced autophagy may play a pro-death role and contribute to the cell death of colorectal cancer cell lines. Furthermore, AKT/mTOR signaling pathway was demonstrated to be a critical mediator in regulating Sal B-induced cell death. Overexpression of AKT by the transfection with AKT plasmid or pretreatment with insulin decreased Sal B-induced autophagy and cell death. Inversely, inhibition of AKT by LY294002 treatment markedly enhanced Sal B-induced autophagy and cell death. Taken together, our results demonstrate, for the first time, that Sal B is a novel autophagy inducer and exerts its antitumor activity as a single agent in colorectal cancer cells through the suppression of AKT/mTOR pathway.


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