BR101801 enhances the radiosensitivity of p53-deficient colorectal cancer cells by inducing G2/M arrest, apoptosis, and senescence in a p53-independent manner.

ABSTRACT: Inhibition of DNA-dependent protein kinase (DNA-PK) in the non-homologous end-joining repair pathway reportedly increases the radiation sensitivity of cancer cells. We have recently reported that BR101801, a novel triple inhibitor of PI3K-gamma (γ), delta (δ), and DNA-PK, functions as an efficient sensitizer of radiation-induced DNA damage in various human solid cancer cells and a xenograft mouse model. Given that the p53 tumor suppressor gene plays an important role in radiotherapeutic efficacy, in the current study, we focused on the impact of the p53 status on BR101801-induced radiosensitization using isogenic HCT116 p53^+/+ and HCT116 p53^-/- human colorectal cancer cell lines. In vitro, HCT116 p53^+/+ and HCT116 p53^-/- human colorectal c

SUBMITTER: Park M 

PROVIDER: S-EPMC10767343 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature