Premium
The Nitric Oxide Prodrug JS‐K Induces Ca 2+ ‐Mediated Apoptosis in Human Hepatocellular Carcinoma HepG2 Cells
Author(s) -
Liu Ling,
Wang Dongmei,
Wang Jiangang,
Wang Shuying
Publication year - 2016
Publication title -
journal of biochemical and molecular toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.526
H-Index - 58
eISSN - 1099-0461
pISSN - 1095-6670
DOI - 10.1002/jbt.21778
Subject(s) - apoptosis , cytochrome c , downregulation and upregulation , mitochondrion , chemistry , bapta , nitric oxide , cytosol , microbiology and biotechnology , apoptotic body , intracellular , biochemistry , biology , organic chemistry , gene , enzyme
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.