Induction of G(1) cell cycle arrest and p27(KIP1) increase by panaxydol isolated from Panax ginseng.
Polyacetylenic compounds of Panax ginseng roots have been shown to inhibit growth of several human malignant tumor cell lines. Panaxydol is known to be one of the cytotoxic polyacetylenic compounds of P. ginseng. In this study, we first showed that panaxydol decreased markedly the proliferation, and to a lesser extent, the number of cells in a human melanoma cell line, SK-MEL-1. Next, the effect of panaxydol on cell cycle progression and its mechanism of action were investigated. Cell cycle analysis revealed that panaxydol inhibited cell cycle progression of a human malignant melanoma cell line, SK-MEL-1, at G(1)-S transition. At the same time, panaxydol increased the protein expression of p27(KIP1) as early as 1 hr after treatment. Cyclin-dependent kinase 2 (Cdk2) activity was decreased in a dose-dependent manner after 24 hr of panaxydol treatment. Protein levels of p21(WAF1), p16(INK4a), p53, pRb (retinoblastoma protein), and E2F-1 were not changed. It was also found that cycloheximide reversed the growth inhibition induced by panaxydol and partially abrogated the increase in p27(KIP1) expression. These results indicate that panaxydol induces G(1) cell cycle arrest by decreasing Cdk2 activity and up-regulating p27(KIP1) protein expression.
Moon
J
J
Graduate School of Biotechnology, Korea University, Seoul, South Korea.
Yu
S J
SJ
Kim
H S
HS
Sohn
J
J
D000480:Alkynes / Q000494:pharmacology*; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D042846:CDC2-CDC28 Kinases; D018797:Cell Cycle Proteins; D002455:Cell Division / Q000187:drug effects; D051357:Cyclin-Dependent Kinase 2; D050760:Cyclin-Dependent Kinase Inhibitor p27; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D053280:Diynes; D005233:Fatty Alcohols / Q000494:pharmacology*; D016193:G1 Phase / Q000187:drug effects*; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000096:biosynthesis* / Q000378:metabolism; D005894:Panax / Q000737:chemistry*; D010946:Plants, Medicinal; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins
D000480:Alkynes; D000972:Antineoplastic Agents, Phytogenic; D018797:Cell Cycle Proteins; D053280:Diynes; D005233:Fatty Alcohols; D008869:Microtubule-Associated Proteins; D011500:Protein Synthesis Inhibitors; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D003609:Dactinomycin; C055778:panaxydol; D003513:Cycloheximide; D017346:Protein Serine-Threonine Kinases; D042846:CDC2-CDC28 Kinases; C495894:CDK2 protein, human; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases