Reactive oxygen species-mediated kinase activation by dihydrotanshinone in tanshinones-induced apoptosis in HepG2 cells.
The role of reactive oxygen species (ROS) and p38 mitogen-activated protein kinases (MAPK) in tanshinones-induced apoptosis was investigated in HepG2 cells in this study. The major tanshinones (cryptotanshinone, dihydrotanshinone, tanshinone I, tanshinone IIA), isolated from Salvia miltiorrhiza, inhibit cell growth and induce caspase-dependent apoptosis concentration-dependently, with dihydrotanshinone being the most potent. All four tanshinones were found to induce ROS generation, but only dihydrotanshinone can induce activation of p38 MAPK. The p38 MAPK activation by dihydrotanshinone was inhibited by N-acetyl cysteine pretreatment. It is thus concluded that ROS-mediated p38 MAPK activation plays a vital role in dihydrotanshinone-induced apoptosis in HepG2 cells.
Lee
Wayne Y W
WY
Department of Pharmacology, The Chinese University of Hong Kong, Shatin, New Territories, SAR, China.
Liu
Ken W K
KW
Yeung
John H K
JH
D045784:Abietanes; D000111:Acetylcysteine / Q000494:pharmacology; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D006528:Carcinoma, Hepatocellular / Q000201:enzymology / Q000473:pathology*; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D045304:Cytochromes c / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D005663:Furans; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008113:Liver Neoplasms / Q000201:enzymology / Q000473:pathology*; D018384:Oxidative Stress / Q000187:drug effects*; D010616:Phenanthrenes / Q000494:pharmacology*; D010766:Phosphorylation; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D021381:Protein Transport; D011725:Pyridines / Q000494:pharmacology; D011809:Quinones; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013997:Time Factors; D051028:bcl-2-Associated X Protein / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*
D045784:Abietanes; D000972:Antineoplastic Agents, Phytogenic; D000975:Antioxidants; C494826:BAX protein, human; D005663:Furans; D007093:Imidazoles; D010616:Phenanthrenes; D047428:Protein Kinase Inhibitors; D011725:Pyridines; D011809:Quinones; D017382:Reactive Oxygen Species; D051028:bcl-2-Associated X Protein; C021751:tanshinone; C000713095:dihydrotanshinone I; C037886:cryptotanshinone; D045304:Cytochromes c; D007770:L-Lactate Dehydrogenase; D011065:Poly(ADP-ribose) Polymerases; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D020169:Caspases; C093642:SB 203580; D000111:Acetylcysteine