title: Tetrandrine induces autophagy and differentiation by activating ROS and Notch1 signaling in leukemia cells.
abstract: 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.
authors: College of Life Sciences, Wuhan University, Wuhan, P. R. China.
authors: Ting
authors: T
authors: Liu
authors: Ministry of Education Laboratory of Combinatorial Biosynthesis and Drug Discovery, College of Pharmacy, Wuhan University, Wuhan, P. R. China.
authors: Qiuxu
authors: Q
authors: Men
authors: College of Life Sciences, Wuhan University, Wuhan, P. R. China.
authors: Guixian
authors: G
authors: Wu
authors: College of Life Sciences, Wuhan University, Wuhan, P. R. China.
authors: Chunrong
authors: C
authors: Yu
authors: College of Life Sciences, Wuhan University, Wuhan, P. R. China.
authors: Zan
authors: Z
authors: Huang
authors: Ministry of Education Laboratory of Combinatorial Biosynthesis and Drug Discovery, College of Pharmacy, Wuhan University, Wuhan, P. R. China.
authors: Xin
authors: X
authors: Liu
authors: College of Life Sciences, Wuhan University, Wuhan, P. R. China.
authors: Wenhua
authors: W
authors: Li
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001343:Autophagy / Q000187:drug effects; D044182:Benzylisoquinolines / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D004365:Drugs, Chinese Herbal / Q000494:pharmacology; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D017382:Reactive Oxygen Species / Q000378:metabolism; D051881:Receptor, Notch1 / Q000378:metabolism*; D015398:Signal Transduction; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D044182:Benzylisoquinolines; D004365:Drugs, Chinese Herbal; C497761:NOTCH1 protein, human; D017382:Reactive Oxygen Species; D051881:Receptor, Notch1; C009438:tetrandrine
keywords: autophagy; differentiation; leukemia cells; tetrandrine