کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5527124 1401566 2016 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Research ArticleArtesunate induces ROS-dependent apoptosis via a Bax-mediated intrinsic pathway in Huh-7 and Hep3B cells
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی تحقیقات سرطان
پیش نمایش صفحه اول مقاله
Research ArticleArtesunate induces ROS-dependent apoptosis via a Bax-mediated intrinsic pathway in Huh-7 and Hep3B cells
چکیده انگلیسی


- ARS induces ROS-dependent apoptosis in Huh-7 cells and Hep3B cells.
- ARS increases intracellular iron ions level in Huh-7/Hep3B cells.
- Bax plays a key role in ARS-induced intrinsic apoptosis 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.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Experimental Cell Research - Volume 347, Issue 2, 1 October 2016, Pages 251-260
نویسندگان
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