Checkpoint kinase 1 inhibition sensitises transformed cells to dihydroorotate dehydrogenase inhibition.

ABSTRACT: Reduction in nucleotide pools through the inhibition of mitochondrial enzyme dihydroorotate dehydrogenase (DHODH) has been demonstrated to effectively reduce cancer cell proliferation and tumour growth. The current study sought to investigate whether this antiproliferative effect could be enhanced by combining Chk1 kinase inhibition. The pharmacological activity of DHODH inhibitor teriflunomide was more selective towards transformed mouse embryonic fibroblasts than their primary or immortalised counterparts, and this effect was amplified when cells were subsequently exposed to PF477736 Chk1 inhibitor. Flow cytometry analyses revealed substantial accumulations of cells in S and G2/M phases, followed by increased cytotoxicity which was characterised by caspase 3-dependent induction of cell d

SUBMITTER: Arnould S 

PROVIDER: S-EPMC5707016 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature