Tetrandrine induces autophagy and differentiation by activating ROS and Notch1 signaling in leukemia cells
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Ting Liu1, Qiuxu Men2, Guixian Wu1, Chunrong Yu1, Zan Huang1, Xin Liu2 and Wenhua Li1
1 College of Life Sciences, Wuhan University, Wuhan, P. R. China
2 Ministry of Education Laboratory of Combinatorial Biosynthesis and Drug Discovery, College of Pharmacy, Wuhan University, Wuhan, P. R. China
Wenhua Li, email:
Xin Liu, email:
Keywords: tetrandrine, leukemia cells, autophagy, differentiation
Received: December 13, 2014 Accepted: February 01, 2015 Published: March 10, 2015
All-trans retinoic acid (ATRA) is a differentiating agent for the treatment of acute promyelocytic leukemia (APL). However, the therapeutic efficacy of ATRA has limitations. Tetrandrine is a traditional Chinese medicinal herb extract with antitumor effects. In this study, we investigated the effects of tetrandrine on human PML-RARα-positive acute promyelocytic leukemia cells. Tetrandrine inhibited tumors in vivo. It induced autophagy and differentiation by triggering ROS generation and activating Notch1 signaling. Tetrandrine induced autophagy and differentiation in M5 type patient primary leukemia cells. The in vivo results indicated that low concentrations of tetrandrine inhibited leukemia cells proliferation and induced autophagy and then facilitated their differentiation, by activating ROS and Notch1 signaling. We suggest that tetrandrine is a potential agent for the treatment of APL by inducing differentiation of leukemia cells.
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