Cells are known to undergo apoptosis when cultured in high serum concentrations. However, the serum factors responsible for this induction of apoptosis have not been identified. The IGF-binding protein-3 (IGFBP-3), a negative growth regulator, is found at concentrations of 5 microgram/ml in serum. We have recently demonstrated that IGFBP-3 induces apoptosis in PC-3 cells, a prostate cancer cell line, at a concentration of 500 ng/ml. In this communication, we demonstrate the role of IGFBP-3 as one of the apoptosis-inducing agents in high serum concentrations. Treatment of PC-3 cells with increasing concentrations (40% to 90%) of intact human serum (HS) resulted in a dose-dependent decrease in cell growth. Valinomycin, an ionophore, was used as a positive control to measure the induction of apoptosis by serum treatment in PC-3 cells. Treatment with 90% serum showed significant suppression of growth (P<0.001) compared with the effect of 10% serum. Treatment with increasing concentrations of HS (40% to 90%) resulted in a dose-dependent increase in apoptosis. Treatment with 90% HS showed a 10-fold increase in apoptotic index compared with cells treated with 10% HS. Treatment of PC-3 cells with IGFs and IGFBP-3-depleted 90% human sera (depleted serum=DS) demonstrated significantly lower levels of apoptosis (50% reduction in the effect of 90% HS) suggesting a role of IGFBP-3 in inducing apoptosis in high serum concentration. Furthermore, treatment with DS supplemented with recombinant IGFBP-3 (500 ng/ml) brought the apoptotic index down close to the level of apoptosis induced by 90% intact serum treatment (P<0.001). However, DS supplemented with physiological concentrations of IGFs (500 ng/ml) showed only partial recovery of cell survival demonstrated by 90% DS. This data indicates that IGFBP-3 is one of the factors in serum that is responsible for high-serum-induced apoptosis.

This article has been cited by other articles:

				L. Peng, P. J. Malloy, J. Wang, and D. Feldman Growth Inhibitory Concentrations of Androgens Up-Regulate Insulin-Like Growth Factor Binding Protein-3 Expression via an Androgen Response Element in LNCaP Human Prostate Cancer Cells Endocrinology, October 1, 2006; 147(10): 4599 - 4607. [Abstract] [Full Text] [PDF]

				I. Peters, I. Tossidou, J. Achenbach, R. Woroniecki, M. Mengel, J.-K. Park, M. Paschy, K. de Groot, H. Haller, and M. Schiffer IGF-Binding Protein-3 Modulates TGF-beta/BMP-Signaling in Glomerular Podocytes J. Am. Soc. Nephrol., June 1, 2006; 17(6): 1644 - 1656. [Abstract] [Full Text] [PDF]

				J. T. Arnold, H. Le, K. K. McFann, and M. R. Blackman Comparative effects of DHEA vs. testosterone, dihydrotestosterone, and estradiol on proliferation and gene expression in human LNCaP prostate cancer cells Am J Physiol Endocrinol Metab, March 1, 2005; 288(3): E573 - E584. [Abstract] [Full Text] [PDF]

				L. Peng, P. J. Malloy, and D. Feldman Identification of a Functional Vitamin D Response Element in the Human Insulin-Like Growth Factor Binding Protein-3 Promoter Mol. Endocrinol., May 1, 2004; 18(5): 1109 - 1119. [Abstract] [Full Text] [PDF]

				A. M. Mikheev, S. A. Mikheeva, B. Liu, P. Cohen, and H. Zarbl A functional genomics approach for the identification of putative tumor suppressor genes: Dickkopf-1 as suppressor of HeLa cell transformation Carcinogenesis, January 1, 2004; 25(1): 47 - 59. [Abstract] [Full Text] [PDF]

				B. S. Schaffer, M.-F. Lin, J. C. Byrd, J. H. Y. Park, and R. G. MacDonald Opposing Roles for the Insulin-Like Growth Factor (IGF)-II and Mannose 6-Phosphate (Man-6-P) Binding Activities of the IGF-II/Man-6-P Receptor in the Growth of Prostate Cancer Cells Endocrinology, March 1, 2003; 144(3): 955 - 966. [Abstract] [Full Text] [PDF]

				R Palmqvist, G Hallmans, S Rinaldi, C Biessy, R Stenling, E Riboli, and R Kaaks Plasma insulin-like growth factor 1, insulin-like growth factor binding protein 3, and risk of colorectal cancer: a prospective study in northern Sweden Gut, May 1, 2002; 50(5): 642 - 646. [Abstract] [Full Text] [PDF]

				O. Kucuk, F. H. Sarkar, W. Sakr, Z. Djuric, M. N. Pollak, F. Khachik, Y.-W. Li, M. Banerjee, D. Grignon, J. S. Bertram, et al. Phase II Randomized Clinical Trial of Lycopene Supplementation before Radical Prostatectomy Cancer Epidemiol. Biomarkers Prev., August 1, 2001; 10(8): 861 - 868. [Abstract] [Full Text] [PDF]