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Title: Artesunate induces apoptosis via a ROS-independent and Bax-mediated intrinsic pathway in HepG2 cells. Author: Qin G, Wu L, Liu H, Pang Y, Zhao C, Wu S, Wang X, Chen T. Journal: Exp Cell Res; 2015 Aug 15; 336(2):308-17. PubMed ID: 26163896. Abstract: This study aims to explore the detail molecular mechanism by which artesunate (ARS), an artemisinin derivative, induces apoptosis in HepG2 cells. ARS induced a loss of mitochondrial transmemberane potential (ΔΨm), phosphatidylserine (PS) externalization, as well as activations of Bax/Bak and caspases indicative of apoptosis induction. Silencing Bax but not Bak significantly inhibited ARS-induced apoptosis, demonstrating the key role of the Bax-mediated intrinsic pathway. Although ARS increased intracellular reactive oxygen species (ROS), ARS-induced apoptosis was neither prevented by pretreatment with ROS scavengers nor potentiated by pretreatment with l-buthionine-sulfoximine (BSO) that enhanced the ARS-induced intracellular ROS generation, demonstrating that ROS was not involved in ARS-induced apoptosis. In addition, ARS did not induce Bid translocation to mitochondria, and the cytotoxicity of ARS was not prevented by silencing Bim, Puma or Mcl-1, but was significantly enhanced by HA14-1 pretreatment, demonstrating that Bcl-2/-xl instead of Bid and Bim as well as Puma may be the upstream factor to regulate the Bax-mediated intrinsic pathway. Collectively, our data demonstrate that ARS induces ROS-independent apoptosis via the Bax-mediated intrinsic pathway in HepG2 cells.[Abstract] [Full Text] [Related] [New Search]