A novel inhibitor of DNA polymerase beta enhances the ability of temozolomide to impair the growth of colon cancer cells.

ABSTRACT: The recent emerging concept to sensitize cancer cells to DNA-alkylating drugs is by inhibiting various proteins in the base excision repair (BER) pathway. In the present study, we used structure-based molecular docking of DNA polymerase beta (Pol-beta) and identified a potent small molecular weight inhibitor, NSC-666715. We determined the specificity of this small molecular weight inhibitor for Pol-beta by using in vitro activities of APE1, Fen1, DNA ligase I, and Pol-beta-directed single-nucleotide and long-patch BER. The binding specificity of NSC-666715 with Pol-beta was also determined by using fluorescence anisotropy. The effect of NSC-666715 on the cytotoxicity of the DNA-alkylating drug temozolomide (TMZ) to colon cancer cells was determined by in vitro clonogenic and in vivo xenogr

SUBMITTER: Jaiswal AS 

PROVIDER: S-EPMC2796282 | biostudies-literature | 2009 Dec

REPOSITORIES: biostudies-literature