ATR kinase inhibition sensitizes quiescent human cells to the lethal effects of cisplatin but increases mutagenesis.

ABSTRACT: The ATR protein kinase is known to protect cells from DNA damage induced during the replicative phase of the cell cycle. Small molecule ATR kinase inhibitors have therefore been developed to improve the effectiveness of DNA damage-based chemotherapy regimens aimed at killing rapidly proliferating tumor cells. However, whether ATR functions in a similar manner in non-replicating cells has not been examined and is important considering the fact that most cells in the body, including cancer stem cells in solid tumors, normally reside in either a quiescent or differentiated non-replicating state. Using cultured human cell lines maintained in a quiescent or slowly growing state in vitro, ATR was found to be activated following treatment with the common anti-cancer drug cisplatin in a manner dep

SUBMITTER: Hutcherson RJ 

PROVIDER: S-EPMC6905468 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature