Ginsenoside RH-2 induces apoptotic cell death in rat C6 glioma via a reactive oxygen- and caspase-dependent but Bcl-X(L)-independent pathway.
We used the rat C6 gliomal cell line to investigate the potential role of ginsenoside Rh2 (G-Rh2) in brain tumor. G-Rh2 induced many apoptotic manifestations in C6 gliomal cells as evidenced by changes in cell morphology, generation of DNA fragmentation, activation of caspase and production of reactive oxygen species (ROS). As a result, cotreatment with antioxidants or a broad-spectrum caspase inhibitor, N-benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone effectively attenuated G-Rh2-induced cell death. However, specific cleavage of poly(ADP-ribose)polymerase into 85 kDa protein was not detected as demonstrated in many other apoptotic paradigms. Expression levels of Bcl-2 and Bax remained unchanged following G-Rh2 treatment. Furthermore, G-Rh2-induced cell death in C6 gliomal cells overexpressing antiapoptotic protein, Bcl-X(L), was comparable to that in parental cells. Taken together, our data indicate that G-Rh2-induced cell death is mediated by the generated ROS and the activation of caspase pathway in a Bcl-X(L)-independent manner.
Kim
H E
HE
Department of Biology, Yonsei University College of Science, Seoul, Korea.
Oh
J H
JH
Lee
S K
SK
Oh
Y J
YJ
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D020169:Caspases / Q000378:metabolism*; D053938:DNA Fragmentation / Q000187:drug effects; D004789:Enzyme Activation; D036145:Ginsenosides; D005910:Glioma; D015151:Immunoblotting; D018384:Oxidative Stress / Q000187:drug effects; D005894:Panax / Q000737:chemistry*; D010946:Plants, Medicinal; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012503:Saponins / Q000494:pharmacology*; D013778:Tetrazolium Salts; D013844:Thiazoles; D014162:Transfection; D014407:Tumor Cells, Cultured; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein
C494828:Bax protein, rat; C494813:Bcl2l1 protein, rat; D036145:Ginsenosides; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D012503:Saponins; D013778:Tetrazolium Salts; D013844:Thiazoles; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein; C055305:ginsenoside Rh2; D020169:Caspases; C022616:thiazolyl blue