[Effect of cisplatin on cell cycle regulators].
An anticancer agent, cisplatin (CDDP), induced G2-phase arrest in PC-9 human cancer cells. To elucidate how CDDP acts on cell-cycle regulation, we analyzed the effect of CDDP on cell-cycle regulators such as P34cdc2 protein kinase. P34cdc2 kinase activity was maximum in G2 phase and decreased after G2/M transition in synchronized PC-9 cells. Evidence for a phosphorylated p34cdc2 complexed with cyclin B was obtained from cells in G2 phase and the p34cdc2 appeared to be dephosphorylated at M phase. After exposure to CDDP in G1 phase, PC-9 cells were arrested at G2 phase. The activation of p34cdc2 was inhibited by CDDP. Cyclin A, B and wee-1 kinase were not affected by the exposure to CDDP. Our data suggested that the effect of CDDP on cell-cycle phase might be regulated by the dephosphorylation of p34cdc2. We hypothesize that inhibition of p34cdc2 dephosphorylation by CDDP is important for its growth-inhibiting properties.
Nishio
K
K
Saijo
N
N
D016203:CDC2 Protein Kinase / Q000187:drug effects* / Q000378:metabolism; D002289:Carcinoma, Non-Small-Cell Lung / Q000473:pathology*; D002453:Cell Cycle / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology*; D016195:G2 Phase; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology*; D010766:Phosphorylation / Q000187:drug effects; D014407:Tumor Cells, Cultured
D016203:CDC2 Protein Kinase; D002945:Cisplatin