Trifluorothymidine Induces Cell Death Independently of p53

Abstract

Trifluorothymidine (TFT), a potent anticancer agent, inhibits thymidylate synthase (TS) and is incorporated into the DNA, both events resulting in cell death. Cell death induction related to DNA damage often involves activation of p53. We determined the role of p53 in TFT cytotoxicity and cell death induction, using, respectively, the sulforhodamine B-assay and FACS analysis, in a panel of cell lines with either wild type, inactive, or mutated p53. Neither TFT cytotoxicity nor cell death induction changed with TFT exposure in cell lines with wt, inactive or mutated p53. Conclusion: sensitivity to TFT is not dependent on the expression of wt p53.

Keywords:

• p53
• trifluorothymidine
• TAS-102
• cell death

This study was supported by Taiho Pharmaceutical Co., Ltd., Tokushima, Japan.