Inhibition of autophagy potentiates anticancer property of 20(S)-ginsenoside Rh2 by promoting mitochondria-dependent apoptosis in human acute lymphoblastic leukaemia cells

// Ting Xia 1, * , Jiancheng Wang 2, * , Yingnan Wang 2 , Yuanyuan Wang 2 , Jianye Cai 2 , Min Wang 1 , Qidan Chen 5 , Jia Song 1 , Ziqi Yu 1 , Wei Huang 1 , Jianpei Fang 3, 4 1 Key Laboratory of Industrial Fermentation Microbiology, Ministry of Education, College of Biotechnology, Tianjin University of Science and Technology, Tianjin, P.R. China 2 Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-Sen University, Guangzhou, P.R. China 3 Department of Pediatrics, Sun Yat-sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, P.R. China 4 Key Laboratory of Malignant Tumor Gene Regulation and Target Therapy of Guangdong Higher Education Institutes, Sun Yat-Sen University, Guangzhou, P.R. China 5 Department of Chemistry and Pharmacy, Zhuhai College, Jilin University, Zhuhai, P.R. China * These authors have contributed equally to this work Correspondence to: Jianpei Fang, e-mail: jpfang2005@163.com Ting Xia, e-mail: xiatingsyu@foxmail.com Keywords: ginsenoside Rh2, acute lymphoblastic leukaemia, autophagy, apoptosis, mitochondria Received: September 10, 2015 Accepted: March 01, 2016 Published: March 23, 2016 ABSTRACT Acute lymphoblastic leukaemia (ALL) is the most prevalent childhood malignancy. Although most children with ALL are cured, there is still a group of patients for which therapy fails owing to severe toxicities and drug resistance. Ginsenoside Rh2 (GRh2), a major bioactive component isolated from Panax ginseng , has been shown to have a therapeutic effect on some tumors. However, the molecular mechanisms of cell death induced by 20(S)-GRh2 in ALL cells remains unclear. In this study, we showed that 20(S)-GRh2 inhibited the cell growth and induced mitochondria-dependent apoptosis and autophagy. But it has no cytotoxic effect on human normal blood cells. Furthermore, autophagy plays a protective role in 20(S)-GRh2-induced apoptosis in ALL cell lines and human primary ALL cells. We demonstrated that either genetic or pharmacologic inhibition of autophagy could be more effective in reducing viability and enhancing 20(S)-GRh2-induced toxicity than 20(S)-GRh2 treatment alone. In addition, inhibition of autophagy could aggravate mitochondrial ROS generation and mitochondrial damage, and then accelerate mitochondria-dependent apoptosis. Taken together, these results suggest that inhibition of autophagy can sensitize ALL cells towards 20(S)-GRh2. The appropriate inhibition of autophagy could provide a powerful strategy to increase the potency of 20(S)-GRh2 as a novel anticancer agent for ALL therapy.