The Nitric Oxide Prodrug JS-K Induces Ca2+-Mediated Apoptosis in Human Hepatocellular Carcinoma HepG2 Cells

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• 作者：Ling Liu ; Dongmei Wang ; Jiangang Wang and Shuying Wang
• 关键词：Hepatocellular Carcinoma ; Nitric Oxide ; JS-K ; Ca2+ ; Apoptosis
• 刊名：Journal of Biochemical and Molecular Toxicology
• 出版年：2016
• 出版时间：April 2016
• 年：2016
• 卷：30
• 期：4
• 页码：192-199
• 全文大小：1824K
• ISSN：1099-0461

文摘

Hepatocellular carcinoma is one of the most common and deadly forms of human malignancies. JS-K, O²-(2, 4-dinitrophenyl) 1- [(4-ethoxycarbonyl) piperazin-1-yl] diazen-1-ium-1, 2-diolate, has the ability to induce apoptosis of tumor cell lines. In the present study, JS-K inhibited the proliferation of HepG2 cells in a time- and concentration-dependent manner and significantly induced apoptosis. JS-K enhanced the ratio of Bax-to-Bcl-2, released of cytochrome c (Cyt c) from mitochondria and the activated caspase-9/3. JS-K caused an increasing cytosolic Ca²⁺ and the loss of mitochondrial membrane potential. Carboxy-PTIO (a NO scavenger) and BAPTA-AM (an intracellular Ca²⁺ chelator) significantly blocked an increasing cytosolic Ca²⁺ in JS-K-induced HepG2 cells apoptosis, especially Carboxy-PTIO. Meanwhile, Carboxy-PTIO and BAPTA-AM treatment both attenuate JS-K-induced apoptosis through upregulation of Bcl-2, downregulation of Bax, reduction of Cyt c release from mitochondria to cytoplasm and inactivation of caspase-9/3. In summary, JS-K induced HepG2 cells apoptosis via Ca²⁺/caspase-3-mediated mitochondrial pathway.