Research Papers:

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

Ting Xia _, Jiancheng Wang, Yingnan Wang, Yuanyuan Wang, Jianye Cai, Min Wang, Qidan Chen, Jia Song, Ziqi Yu, Wei Huang and Jianpei Fang

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Oncotarget. 2016; 7:27336-27349. https://doi.org/10.18632/oncotarget.8285

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Ting Xia1,*, Jiancheng Wang2,*, Yingnan Wang2, Yuanyuan Wang2, Jianye Cai2, Min Wang1, Qidan Chen5, Jia Song1, Ziqi Yu1, Wei Huang1, Jianpei Fang3,4

1Key Laboratory of Industrial Fermentation Microbiology, Ministry of Education, College of Biotechnology, Tianjin University of Science and Technology, Tianjin, P.R. China

2Center 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

3Department of Pediatrics, Sun Yat-sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, P.R. China

4Key Laboratory of Malignant Tumor Gene Regulation and Target Therapy of Guangdong Higher Education Institutes, Sun Yat-Sen University, Guangzhou, P.R. China

5Department 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: [email protected]

Ting Xia, e-mail: [email protected]

Keywords: ginsenoside Rh2, acute lymphoblastic leukaemia, autophagy, apoptosis, mitochondria

Received: September 10, 2015    Accepted: March 01, 2016    Published: March 23, 2016


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.

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