Transforming growth factor beta 1-induced apoptosis in human ovarian carcinoma cells: protection by the antioxidant N-acetylcysteine and bcl-2.

We have previously shown that transforming growth factor beta 1 (TGF-beta 1) inhibits growth and induces apoptosis in NIH-OVCAR-3 ovarian adenocarcinoma cells. In this study, we investigated the role of the reactive oxygen species in the TGF-beta 1 signaling pathways. We found that both TGF-beta 1 and an oxidant, hydrogen peroxide, rapidly increase the expression of c-fos and c-jun genes and induce cell death by apoptosis; these effects are inhibited by the antioxidant N-acetylcysteine. In contrast, N-acetylcysteine did not influence TGF-beta 1-mediated cell cycle arrest at the G1-S transition. TGF-beta 1 down-regulated the endogenous expression of the anti-apoptotic bcl-2 gene, and overexpression of this gene inhibited TGF-beta 1-induced apoptosis. Taken together, these results suggest that TGF-beta 1 activates multiple signaling pathways in the NIH-OVCAR-3 cell line and that the reactive oxygen species play a role in the early gene responses and apoptosis induced by TGF-beta 1.