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.
Lafon
C
C
Laboratoire de Pharmacologie et Toxicologie Fondamentales, Centre National de la Recherche Scientifique, Toulouse, France.
Mathieu
C
C
Guerrin
M
M
Pierre
O
O
Vidal
S
S
Valette
A
A
D000111:Acetylcysteine / Q000494:pharmacology*; D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism*; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D015152:Blotting, Northern; D015153:Blotting, Western; D002455:Cell Division / Q000187:drug effects; D053938:DNA Fragmentation / Q000187:drug effects / Q000502:physiology; D005260:Female; D016762:Genes, fos / Q000187:drug effects / Q000502:physiology; D016758:Genes, jun / Q000187:drug effects / Q000502:physiology; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D010051:Ovarian Neoplasms / Q000235:genetics / Q000378:metabolism*; D018384:Oxidative Stress / Q000502:physiology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000187:drug effects / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis; D013997:Time Factors; D014162:Transfection; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D006861:Hydrogen Peroxide; D000111:Acetylcysteine