Insulin-like growth factor I (IGF-I) and IGF binding protein-1 modulate prostate cancer cell growth and apoptosis: possible mediators for the effects of diet and exercise on cancer cell survival.
Previous studies showed that serum from men consuming a low fat diet and undergoing exercise intervention (DE) reduced LNCaP cell growth and induced apoptosis in vitro. DE also decreased serum IGF-I and increased serum IGF binding protein-1 (IGFBP-1). The present study evaluates the effects of IGF-I and IGFBP-1 on growth and apoptosis of prostate cancer cells in vitro. When IGF-I was added to the post-DE serum, the reduction in LNCaP cell growth and the induction of apoptosis in medium containing post-DE serum alone were reversed. When IGFBP-1 was added to the pre-DE serum samples, LNCaP cell growth was reduced, and apoptosis was induced. IGF-I, long-R(3)-IGF-I (only binds IGF-I receptor), AL(31)Leu(60)-IGF-I (only binds IGFBPs), antihuman IGF-I receptor antibodies, and IGFBP-1 were then added to LNCaP cultures to determine the independent effects of IGF-I and IGFBP-1 on cell growth. Collectively, the results using these agents show that IGF-I and IGFBP-1 exert opposing effects on LNCaP cell growth and apoptosis, and IGFBP-1 acts mainly through an IGF-dependent mechanism. DE results in a decrease in serum IGF-I with increased IGFBP-1 in vivo that is associated with apoptosis and reduced LNCaP and LAPC-4 prostate cancer cell growth in vitro.
Ngo
Tung H
TH
Department of Physiological Science, University of California, Los Angeles, California 90095, USA.
Barnard
R James
RJ
Leung
Pak-Shan
PS
Cohen
Pinchas
P
Aronson
William J
WJ
D017209:Apoptosis / Q000187:drug effects; D001798:Blood Proteins / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D018752:Diet, Fat-Restricted; D004041:Dietary Fats / Q000494:pharmacology; D015444:Exercise; D006801:Humans; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000097:blood / Q000494:pharmacology*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism / Q000494:pharmacology*; D008297:Male; D011471:Prostatic Neoplasms; D014407:Tumor Cells, Cultured / Q000166:cytology / Q000187:drug effects
D001798:Blood Proteins; D004041:Dietary Fats; D018970:Insulin-Like Growth Factor Binding Protein 1; D007334:Insulin-Like Growth Factor I