The Nitric Oxide Prodrug JS‐K Induces Ca2+‐Mediated Apoptosis in Human Hepatocellular Carcinoma HepG2 Cells |
| |
Authors: | Ling Liu Dongmei Wang Jiangang Wang Shuying Wang |
| |
Institution: | 1. Department of Pharmacy, Medical College, Henan University of Science and Technology, Luoyang, People's Republic of China;2. Department of Pathogen Biology, Medical College, Henan University of Science and Technology, Luoyang, People's Republic of China |
| |
Abstract: | 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. |
| |
Keywords: | Hepatocellular Carcinoma Nitric Oxide JS‐K Ca2+ Apoptosis |
|
|