Artesunate induces ROS-dependent apoptosis via a Bax-mediated intrinsic pathway in Huh-7 and Hep3B cells.
Artesunate (ARS), an artemisinin derivative, has been demonstrated to possess antitumor activity in various human tumor cells. This study aims to investigate the molecular mechanism by which ARS induces apoptosis in human hepatocellular carcinoma cells (Huh-7 and Hep3B cells). ARS effectively induced externalization of phosphatidylserine (PS), depolarization of mitochondrial membrane, release of cytochrome c from mitochondria, and activation of caspase-9 and 3, characteristics of the intrinsic apoptosis. Pretreatment with antioxidant N-Acetyle-Cysteine (NAC) completely blocked ARS-induced reactive oxygen species (ROS) generation and apoptosis in the two cell lines. ARS increased cellular iron ions level in Huh-7/Hep3B cells, but decreased cellular iron ions level in HepG2 cells. Pifithrin-alpha (PFT), an inhibitor of p53, significantly enhanced ARS-induced cytotoxicity in HepG2 cells, and the forced expression of wild-type p53 significantly enhanced ARS-induced cytotoxicity in Hep3B cells. In addition, ARS induced translocation and activation of the proapoptotic Bax, and silencing Bax remarkably inhibited ARS-induced apoptosis and ΔΨm collapse in Huh-7 and Hep3B cells, demonstrating the key role of Bax in ARS-induced apoptosis. Collectively, our data demonstrate that ARS induces ROS-dependent apoptosis via a Bax-mediated intrinsic pathway in Huh-7 and Hep3B cells.
['Pang|Yilin|Y|', 'Qin|Guiqi|G|', 'Wu|Liping|L|', 'Wang|Xiaoping|X|', 'Chen|Tongsheng|T|']
D017209:Apoptosis D037621:Artemisinins D000077332:Artesunate D045744:Cell Line, Tumor D006801:Humans D007477:Ions D007501:Iron D008954:Models, Biological D017382:Reactive Oxygen Species D015398:Signal Transduction D013997:Time Factors D016159:Tumor Suppressor Protein p53 D050998:bcl-2 Homologous Antagonist-Killer Protein D051028:bcl-2-Associated X Protein
Artesunate Apoptosis Hepatocellular carcinoma cells ROS Bax Caspases