Pharmacological targeting of c-FLIP_L and Bcl-2 family members promotes apoptosis in CD95L-resistant cells.

ABSTRACT: The development of efficient combinatorial treatments is one of the key tasks in modern anti-cancer therapies. An apoptotic signal can either be induced by activation of death receptors (DR) (extrinsic pathway) or via the mitochondria (intrinsic pathway). Cancer cells are characterized by deregulation of both pathways. Procaspase-8 activation in extrinsic apoptosis is controlled by c-FLIP proteins. We have recently reported the small molecules FLIPinB/FLIPinBγ targeting c-FLIP_L in the caspase-8/c-FLIP_L heterodimer. These small molecules enhanced caspase-8 activity in the death-inducing signaling complex (DISC), CD95L/TRAIL-induced caspase-3/7 activation and subsequent apoptosis. In this study to increase the pro-apoptotic effects of FLIPinB/FLIPinBγ and enhance its th

SUBMITTER: Konig C 

PROVIDER: S-EPMC7705755 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature