Inhibition of store-operated channels by carboxyamidotriazole sensitizes ovarian carcinoma cells to anti-Bclx_L strategies through Mcl-1 down-regulation.

ABSTRACT: The anti-apoptotic proteins Bcl-x_L and Mcl-1 have been identified to play a pivotal role in apoptosis resistance in ovarian cancer and constitute key targets for innovative therapeutic strategies. Although BH3-mimetics (i.e. ABT-737) potently inhibit Bcl-x_L activity, targeting Mcl-1 remains a hurdle to the success of these strategies. Calcium signaling is profoundly remodeled during carcinogenesis and was reported to activate the signaling pathway controlling Mcl-1 expression. In this context, we investigated the effect of carboxyamidotriazole (CAI), a calcium channel inhibitor used in clinical trials, on Mcl-1 expression. CAI had an anti-proliferative effect on ovarian carcinoma cell lines and strongly down-regulated Mcl-1 expression. It inhibited store-operated calc

SUBMITTER: Bonnefond ML 

PROVIDER: S-EPMC6188062 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature