Ginsenoside Rh2 induces apoptosis via activation of caspase-1 and -3 and up-regulation of Bax in human neuroblastoma.
In human neuroblastoma SK-N-BE(2) cells undergoing apoptotic death induced by ginsenoside Rh2, a dammarane glycoside that was isolated from Panax ginseng C. A. Meyer, caspase-1 and caspase-3 were activated. The expression of Bax was increased in the cells treated with ginsenoside Rh2, whereas Bcl-2 expression was not altered. Treatment with caspase-1 inhibitor, Ac-YVAD-CMK, or caspase-3 inhibitor, Z-DEVD-FMK, partially inhibited ginsenoside Rh2-induced cell death but almost suppressed the cleavage of the 116 kDa PARP into a 85 kDa fragment. When the levels of p53 were examined in this process, p53 accumulated rapidly in the cells treated early with ginsenoside Rh2. These results suggest that activation of caspase-1 and -3 and the up-regulation of Bax are required in order for apoptotic death of SK-N-BE(2) cells to be induced by ginsenoside Rh2, and p53 plays an important role in the pathways to promote apoptosis.
Kim
Young-Sook
YS
KT&G Central Research Institute, Yuseong-gu, Daejeon 305-805, Korea. yskim@ktng.com
Jin
Sung-Ha
SH
D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D020170:Caspase 1 / Q000378:metabolism*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism*; D045744:Cell Line, Tumor; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D036145:Ginsenosides / Q000302:isolation & purification / Q000494:pharmacology*; D006801:Humans; D009447:Neuroblastoma / Q000201:enzymology*; D005894:Panax; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis* / Q000235:genetics; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology; D051028:bcl-2-Associated X Protein
C494826:BAX protein, human; D036145:Ginsenosides; D010936:Plant Extracts; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; C055305:ginsenoside Rh2; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; D020170:Caspase 1