Cdk2 activity is associated with depolarization of mitochondrial membrane potential during apoptosis.
In this study we show that panaxadiol, a ginseng saponin with a dammarane skeleton, induces apoptotic cell death by depolarization of mitochondrial membrane potential in human hepatoma SK-HEP-1 cells. Sequential activation of caspases-9, -3, and -7, but not of caspase-8, occurs after mitochondrial membrane depolarization and cytochrome c release from the mitochondria of panaxadiol-treated cells. Moreover, Cdk2 kinase activity, but not Cdc2 kinase activity, is markedly upregulated in the early stages of apoptosis. Olomoucine or roscovitine, specific Cdks inhibitors, effectively prevent mitochondrial membrane depolarization as well as apoptotic cell death in panaxadiol-treated cells. Thus, panaxadiol-treatment induces cell death-dependent activation of Cdk2 kinase activity, which is functionally associated with depolarization of mitochondrial membrane potential and subsequent cytochrome c release.
Jin
Ying Hua
YH
College of Pharmacy, The Research Institute for Pharmaceutical Sciences, Seoul National University, Seoul 151-742, Republic of Korea.
Yim
Hyungshin
H
Park
Jeong Hill
JH
Lee
Seung Ki
SK
D000970:Antineoplastic Agents / Q000737:chemistry / Q000633:toxicity*; D017209:Apoptosis; D042846:CDC2-CDC28 Kinases; D006528:Carcinoma, Hepatocellular / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology; D020169:Caspases / Q000378:metabolism; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases / Q000378:metabolism*; D003574:Cytochrome c Group / Q000378:metabolism; D036145:Ginsenosides / Q000737:chemistry / Q000633:toxicity*; D006801:Humans; D007425:Intracellular Membranes / Q000201:enzymology; D008113:Liver Neoplasms / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology; D008564:Membrane Potentials / Q000187:drug effects; D008928:Mitochondria / Q000201:enzymology* / Q000502:physiology; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D014315:Triterpenes / Q000737:chemistry / Q000633:toxicity*; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
D000970:Antineoplastic Agents; D003574:Cytochrome c Group; D036145:Ginsenosides; D014315:Triterpenes; C004564:panaxadiol; D017346:Protein Serine-Threonine Kinases; D042846:CDC2-CDC28 Kinases; C495894:CDK2 protein, human; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases; D020169:Caspases