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

// Zhao Jing 1, 2, * , Weiqiang Fei 2, * , Jichun Zhou 3, * , Lumin Zhang 2 , Liuxi Chen 1 , Xiaomin Zhang 1 , Xiao Liang 4 , Jiansheng Xie 2 , Yong Fang 1, 2 , Xinbing Sui 1, 2 , Weidong Han 1, 2 , Hongming Pan 1, 2 1 Department of Medical Oncology, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China 2 Biomedical Research Center and Key Laboratory of Biotherapy of Zhejiang Province, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China 3 Department of Surgical Oncology, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China 4 Department 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: hzzju@aliyun.com Weidong Han, email: hanwd@126.com Hongming Pan, email: drpanhm@aliyun.com 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.