Reactive oxygen species mediated ginsenoside Rg3- and Rh2-induced apoptosis in hepatoma cells through mitochondrial signaling pathways.
Panax ginseng (P. ginseng) has anti-cancer effects in several cancer models. Ginsenosides are the main bioactive components in P. ginseng. Korean red ginseng (KRG) extract can potently kill various cancer cells and ginsenosides Rg3 (GRg3) and Rh2 (GRh2) are the primary ginsenosides in KRG. This study was carried out to examine whether KRG and its primary ginsenosides (GRg3 and GRh2) affect apoptosis of human hepatocellular carcinoma cells (Hep3B). KRG, GRg3 and GRh2 have obvious cytotoxic and apoptotic effects in Hep3B cells as evidenced by a decrease in cell viability and mitochondria membrane potential, but an increase in LDH release. In the mitochondria-mediated apoptosis pathway, KRG, GRg3 and GRh2 have the ability to stimulate the release of mitochondrial cytochrome c, activation of caspase-3 and Bax protein, inhibition of Bcl-2 protein and production of intracellular reactive oxygen species in Hep3B cells. These results suggest that KRG, GRg3 and GRh2 may induce apoptosis by direct activation of the mitochondrial pathway.
Department of Pharmacology and Toxicology, College of Veterinary Medicine, Chonbuk National University, Jeonju 561-756, Republic of Korea.
Hye-Min
HM
Park
Shang-Jin
SJ
Kim
Jin-Shang
JS
Kim
Hyung-Sub
HS
Kang
D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D036145:Ginsenosides / Q000494:pharmacology*; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*
D036145:Ginsenosides; D017382:Reactive Oxygen Species; C097367:ginsenoside Rg3; C055305:ginsenoside Rh2