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

Abstract:

BACKGROUND:Chkl is a checkpoint gene that is activated after DNA damage. It phosphorylates and inactivates Cdc25C at the late G2 phase. The inactivation of Cdc25C and consequently, the inactivation of Cdc2, are required for the G2 arrest induced by DNA damage. METHODS:We treated 184B5 cell line and its E6 transformed cell lines with adriamycin in the presence of staurosporine or UCNO1 and examined G2 arrest and cell death. RESULTS:We found that adriamycin induced a p53 and p21 response as well as a G1 arrest in 184B5 cells, but not in its E6 transformed cells. Staurosporine or UCNO1 abrogated the G2 arrest induced by adriamycin in both cell lines. In addition, staurosporine or UCNO1 specifically sensitized p53 incompetent cells to adriamycin. CONCLUSION:G2/M checkpoint abrogators can potentially enhance the cytotoxic effect of conventional chemotherapeutic reagents specifically to tumor cells.

journal_name

Anticancer Res

journal_title

Anticancer research

authors

Luo Y,Rockow-Magnone SK,Joseph MK,Bradner J,Butler CC,Tahir SK,Han EK,Ng SC,Severin JM,Gubbins EJ,Reilly RM,Rueter A,Simmer RL,Holzman TF,Giranda VL

subject

Has Abstract

pub_date

2001-01-01 00:00:00

pages

23-8

issue

1A

eissn

0250-7005

issn

1791-7530

journal_volume

21

pub_type

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