Diol- and triol-type ginseng saponins potentiate the apoptosis of NIH3T3 cells exposed to methyl methanesulfonate.
In this study we investigated the effect of ginseng saponins on the p53-dependent apoptosis in NIH3T3 cells exposed to methyl methanesulfonate (MMS), an alkylating agent. Trypan blue exclusion assay, cell morphology studies, and apoptotic index determined by acridine orange staining showed that the postincubation of MMS-exposed cells in medium containing diol- (PD) or triol-type (PT) ginseng saponins potentiate the apoptotic cell death. FACS analysis indicated that the increased apoptotic cell population in the saponin-postincubation group was accompanied by the accumulation of cells in G0/G1 phase. By Western blot analyses it was demonstrated that postincubation of saponins increases the expression of p53 and p21 in MMS-exposed cells but decreased that of CDK2, cyclin E and D1, and PCNA. The upregulation of p53 and p21 and downregulation of CDK2 was shown to be p53-dependent in experiments using the p53 antisense oligonucleotide. These results suggest that ginseng saponins contain components potentiating the apoptosis of MMS-exposed NIH3T3 cells via p53 and p21 activation, accompanied with by downregulation of cell cycle-related protein expression.
Hwang
Sung Jin
SJ
Division of Biological Science, Wonkwang University, Iksan, Chonbuk 570-749, South Korea.
Cha
Jae Young
JY
Park
Seh Geun
SG
Joe
Gi Jung
GJ
Kim
Hyung Min
HM
Moon
Hyung Bae
HB
Jeong
Se Jin
SJ
Lee
Jung Sup
JS
Shin
Dong Hwa
DH
Ko
Sung Ryong
SR
Park
Jong Kun
JK
D016475:3T3 Cells; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D042846:CDC2-CDC28 Kinases; D018797:Cell Cycle Proteins / Q000378:metabolism; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D004357:Drug Synergism; D005434:Flow Cytometry; D008741:Methyl Methanesulfonate / Q000633:toxicity*; D051379:Mice; D009153:Mutagens / Q000633:toxicity*; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D015689:Oncogene Protein p21(ras) / Q000378:metabolism; D005894:Panax / Q000737:chemistry*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D012503:Saponins / Q000737:chemistry / Q000494:pharmacology*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D018797:Cell Cycle Proteins; D009153:Mutagens; D016376:Oligonucleotides, Antisense; D012503:Saponins; D016159:Tumor Suppressor Protein p53; D008741:Methyl Methanesulfonate; D017346:Protein Serine-Threonine Kinases; D042846:CDC2-CDC28 Kinases; C495893:Cdk2 protein, mouse; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases; D015689:Oncogene Protein p21(ras)