Mitochondrial permeabilization engages NF-κB-dependent anti-tumour activity under caspase deficiency.

ABSTRACT: Apoptosis represents a key anti-cancer therapeutic effector mechanism. During apoptosis, mitochondrial outer membrane permeabilization (MOMP) typically kills cells even in the absence of caspase activity. Caspase activity can also have a variety of unwanted consequences that include DNA damage. We therefore investigated whether MOMP-induced caspase-independent cell death (CICD) might be a better way to kill cancer cells. We find that cells undergoing CICD display potent pro-inflammatory effects relative to apoptosis. Underlying this, MOMP was found to stimulate NF-κB activity through the downregulation of inhibitor of apoptosis proteins. Strikingly, engagement of CICD displays potent anti-tumorigenic effects, often promoting complete tumour regression in a manner dependent on intact immuni

SUBMITTER: Giampazolias E 

PROVIDER: S-EPMC5624512 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature