Induction of colonic epithelial cell apoptosis by p47-dependent oxidants

Exogenous oxidants appear capable of initiating both proliferative and death signals, but the role of endogenous oxidants in either tumorigenesis or tumor suppression is unclear. We found that expression of the NAD(P)H oxidase adapter p47^phox was suppressed in human colon carcinoma specimens relative to adjacent normal colon. Overexpression of p47^phox increased apoptosis in colon cancer cell lines independent of p53 and mismatch-repair competency. p47^phox was found to interact with the c-Abl adapter Abl interactor-1 (ABI-1), and p47^phox coprecipitated with both ABI-1 and c-Abl. Ectopic expression of p47^phox in colon cancer cells increased oxidant production with phosphorylation and activation of nuclear c-Abl and consequent apoptosis. Colonic epithelial p47^phox may be specifically targeted to a c-Abl-containing complex that serves a physiologic tumor suppressing function.