Abrogation of G2 checkpoint specifically sensitize p53 defective cells to cancer chemotherapeutic agents

Background: Chkl is a checkpoint gene that is activated after DNA damage, I t phosphorylates and inactivates Cdc25C at the late G2 phase. The inactivat ion of Cdc25C and consequently, the inactivation of Cdc2, are required for the G2 arrest induced by DNA damage. Methods: We treated 184B5 cell line an d its E6 transformed cell lines with adriamycin in the presence of staurosp orine or UCNO1 and examined induced a p53 and p21 response as well as a G1 arrest in 184B5 cells, but not in its E6 transformed cells. Staurosporine o r UCNO1 abrogated the G2 arrest induced by adriamycin in both cell lines. I n addition staurosporine or UCNO1 specifically sensitized p52 incompetent c ells to adriamycin. Conclusion: G2/M checkpoint abrogators can potentially enhance the cytotoxic effect of conventional chemotherapeutic reagents spec ifically to tumor cells.