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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

Departments of Physiological Science (T.H.N., R.J.B., P.-S.L.), Pediatrics (P.C.), and Urology (W.J.A.), University of California, Los Angeles, California 90095

Address all correspondence and requests for reprints to: R. James Barnard, Ph.D., Department of Physiological Science, University of California, 4303 Life Science Building, 621 Charles Young Drive South, Los Angeles, California 90095. E-mail: jbarnard{at}physci.ucla.edu.

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-R³-IGF-I (only binds IGF-I receptor), AL³¹Leu⁶⁰-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.

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