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

Cell Growth Differ. 1996 Aug;7(8):1095-104.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcysteine / pharmacology*
  • Adenocarcinoma / genetics
  • Adenocarcinoma / metabolism*
  • Apoptosis / drug effects
  • Apoptosis / physiology*
  • Blotting, Northern
  • Blotting, Western
  • Cell Division / drug effects
  • DNA Fragmentation / drug effects
  • DNA Fragmentation / physiology
  • Female
  • Genes, fos / drug effects
  • Genes, fos / physiology
  • Genes, jun / drug effects
  • Genes, jun / physiology
  • Humans
  • Hydrogen Peroxide / pharmacology
  • Ovarian Neoplasms / genetics
  • Ovarian Neoplasms / metabolism*
  • Oxidative Stress / physiology
  • Proto-Oncogene Proteins c-bcl-2 / drug effects
  • Proto-Oncogene Proteins c-bcl-2 / genetics*
  • RNA, Messenger / analysis
  • Time Factors
  • Transfection
  • Transforming Growth Factor beta / pharmacology*
  • Tumor Cells, Cultured

Substances

  • Proto-Oncogene Proteins c-bcl-2
  • RNA, Messenger
  • Transforming Growth Factor beta
  • Hydrogen Peroxide
  • Acetylcysteine