Enhanced Cytotoxicity on Cancer Cells by Combinational Treatment of PARP Inhibitor and 5-Azadeoxycytidine Accompanying Distinct Transcriptional Profiles.

ABSTRACT: Poly(ADP-ribose) polymerase (PARP) is involved in DNA repair and chromatin regulation. 5-Aza-2'-deoxycytidine (5-aza-dC) inhibits DNA methyltransferases, induces hypomethylation, blocks DNA replication, and causes DNA single strand breaks (SSBs). As the PARP inhibitor is expected to affect both DNA repair and transcriptional regulations, we investigated the effect of combinational use of PARP inhibitors on cytotoxicity of 5-aza-dC in human cancer cell lines. The combinational treatment of 5-aza-dC and PARP inhibitor PJ-34 exhibited a stronger cytotoxicity compared with their treatment alone in blood cancer HL-60, U937, and colon cancer HCT116 and RKO cells. Treatment with 5-aza-dC but not PJ-34 caused SSBs in HCT116 cell lines. Global genome DNA demethylation was observed after treatment w

SUBMITTER: Araki T 

PROVIDER: S-EPMC9454563 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature