Apoptotic effects of ginsenoside Rh2 on human malignant melanoma A375-S2 cells.
OBJECTIVE
To study the mechanism of ginsenoside-Rh2 (G-Rh2)-induced growth inhibition of A375-S2 cells.


METHODS
A375-S2 cell viability and the effect of caspase inhibitors on G-Rh2-induced apoptosis were measured by crystal violet assay. Changes in cellular morphology were observed by phase-contrast microscopy. Apoptosis-specific nucleosomal DNA fragmentation was assayed by agarose gel electrophoresis. Cell cycle distribution was measured by flow cytometry.


RESULTS
G-Rh2 inhibited the A375-S2 cell growth in concentration- and time-dependent manners. Caspase family inhibitor, z-Val-Ala-Asp-fluoromethylketone (z-VAD-fmk), caspase-3 inhibitor, z-Asp-Glu-Val-Asp-fluoromethylketone (z-DEVD-fmk), and caspase-8 inhibitor, z-Ile-Glu-Asp-fluoromethylketone (z-IETD-fmk), partially inhibited G-Rh2-induced apoptosis. But caspase-1 inhibitor, Ac-Tyr-Val-Ala-Asp-chloromethyl-ketone (Ac-YVAD-cmk), did not antagonize G-Rh2 induced-cell death.


CONCLUSIONS
G-Rh2 suppresses the growth of A375-S2 cells in vitro by inducing apoptosis. G-Rh2-induced apoptosis is partially dependent on caspase-8 and caspase-3 pathway in A375-S2 cells. Other apoptotic pathways might be also related to the induction of apoptosis by G-Rh2.
Fei
Xiao-Fang
XF
China Japan Research Institute of Medical Sciences, Affiliated Hospital of Changchun College of Traditional Chinese Medicine, Changchun 130021, China.
Wang
Ben-Xiang
BX
Tashiro
Shinichi
S
Li
Tie-Jin
TJ
Ma
Ji-Sheng
JS
Ikejima
Takashi
T
D017209:Apoptosis; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9; D061945:Caspase Inhibitors; D002455:Cell Division / Q000187:drug effects; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D036145:Ginsenosides / Q000494:pharmacology*; D006801:Humans; D008545:Melanoma / Q000473:pathology*; D009842:Oligopeptides / Q000494:pharmacology; D005894:Panax / Q000737:chemistry*; D012878:Skin Neoplasms / Q000473:pathology; D014407:Tumor Cells, Cultured
D061945:Caspase Inhibitors; D015853:Cysteine Proteinase Inhibitors; D004365:Drugs, Chinese Herbal; D036145:Ginsenosides; D009842:Oligopeptides; C110772:benzoylcarbonyl-aspartyl-glutamyl-valyl-aspartyl-fluoromethyl ketone; C403753:benzyloxycarbonyl-isoleucyl-glutamyl-threonyl-aspartic acid fluoromethyl ketone; C055305:ginsenoside Rh2; C505407:CASP3 protein, human; C505530:CASP8 protein, human; C506433:CASP9 protein, human; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9