Cellular effects of olomoucine in human lymphoma cells differing in p53 function

Olomoucine, a purine derivative, inhibits multiple cyclin-dependent kinases that play important roles in regulating the G1/S and G2/M transitions of t he cell cycle. In this study we investigated the cellular effects of olomou cine in two human Burkitt's lymphoma cell lines, WMN (containing wild-type p53) and CA46 (containing mutant p53), and found that in consistency with i ts ability to block the activity of cyclin E/Cdk2 and cyclin B1/Cdc2 kinase s, olomoucine caused cell cycle arrest at both G1/S and G2/S boundaries. Mo reover, cell cycle arrest occurred equally well in these two cell lines bea ring different p53 gene status, suggesting that p53 was not responsible for the cell cycle arrest by olomoucine. A similar p53-independent fashion was also observed in the cytotoxic potency and apoptosis induction of olomouci ne, in contrast to ionizing radiation which caused more cytotoxic activity and apoptosis in the WMN cell line bearing wild-type p53 compared with CA46 cells bearing mutant p53. Such p53-independent cytotoxicity of olomoucine was also confirmed in other human Burkitt's lymphoma and lymphoid cell line s containing wild-type and mutant p53. Therefore, our results give an impet us to continued research into olomoucine that might be a very useful chemot herapeutic strategy in the treatment of patients with mutant p53 tumors, at least in lymphoma patients. Copyright (C) 1999 S. Karger AG, Basel.