The Nitric Oxide Prodrug JS‐K Induces Ca2+‐Mediated Apoptosis in Human Hepatocellular Carcinoma HepG2 Cells. Issue 4 (30th November 2015)

• Record Type: Journal Article
• Authors: Liu, Ling; Wang, Dongmei; Wang, Jiangang; Wang, Shuying
• Is Part Of: Journal of biochemical and molecular toxicology. Volume 30:Issue 4(2016:Apr.)
• Page Start: 192
• Page End: 199
• Publication Date: 2015-11-30
• Subjects: Hepatocellular Carcinoma -- Nitric Oxide -- JS‐K -- Ca2+ -- Apoptosis; Biochemistry -- Periodicals; Molecular biology -- Periodicals; Toxicology -- Periodicals; 574
• DOI: 10.1002/jbt.21778
• Languages: English
• ISSNs: 1095-6670

Abstract

ABSTRACT: Hepatocellular carcinoma is one of the most common and deadly forms of human malignancies. JS‐K, O 2 ‐(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 Ca 2+ and the loss of mitochondrial membrane potential. Carboxy‐PTIO (a NO scavenger) and BAPTA‐AM (an intracellular Ca 2+ chelator) significantly blocked an increasing cytosolic Ca 2+ 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 Ca 2+ /caspase‐3‐mediated mitochondrial pathway.