title: The Nitric Oxide Prodrug JS-K Induces Ca(2+)-Mediated Apoptosis in Human Hepatocellular Carcinoma HepG2 Cells.
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.
authors.affiliation: Department of Pharmacy, Medical College, Henan University of Science and Technology, Luoyang, 471003, People's Republic of China. liuling921@126.com.
authors.forename: Ling
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Pathogen Biology, Medical College, Henan University of Science and Technology, Luoyang, 471003, People's Republic of China.
authors.forename: Dongmei
authors.initials: D
authors.lastname: Wang
authors.affiliation: Department of Pharmacy, Medical College, Henan University of Science and Technology, Luoyang, 471003, People's Republic of China.
authors.forename: Jiangang
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Pharmacy, Medical College, Henan University of Science and Technology, Luoyang, 471003, People's Republic of China.
authors.forename: Shuying
authors.initials: S
authors.lastname: Wang
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D001391:Azo Compounds / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000473:pathology*; D049109:Cell Proliferation / Q000187:drug effects; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000473:pathology*; D009569:Nitric Oxide / Q000378:metabolism / Q000494:pharmacology*; D010879:Piperazines / Q000494:pharmacology*; D011355:Prodrugs / Q000494:pharmacology*
chemical_list: D001391:Azo Compounds; C474958:O(2)-(2,4-dinitrophenyl) 1-((4-ethoxycarbonyl)piperazin-1-yl)diazen-1-ium-1,2-diolate; D010879:Piperazines; D011355:Prodrugs; D009569:Nitric Oxide; D002118:Calcium
keywords: Apoptosis; Ca2+; Hepatocellular Carcinoma; JS-K; Nitric Oxide