Journal
ONCOTARGET
Volume 6, Issue 10, Pages 7992-8006Publisher
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.3505
Keywords
tetrandrine; leukemia cells; autophagy; differentiation
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Funding
- National Basic Research Program of China [2014CB910600]
- National Natural Science Foundation of China [81273540, 31400155]
- Program for New Century Excellent Talents in University of Ministry of Education of China [NCET-13-0436]
- Fundamental Research Funds for the Central Universities [2042014kf0236]
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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-RARa-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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