Current investigations center on the effects of selected androgenic (DHEA), estrogenic (phytoestrogens) or other (carnitine) dietary supplements and/or botanical agents on neoplastic prostate stromal and epithelial cell growth, and cell-cell signaling. As a precursor to both estrogen and testosterone, DHEA may pose a potential cancer risk in hormone responsive tissues such as the prostate. We hypothesize that DHEA administration exerts its principal effects on prostate cancer cells via androgenic effects like those of testosterone (T) and dihydrotestosterone (DHT). We speculate that these effects include modulation of expression of IGF-axis proteins in prostate epithelial cells growing in monoculture, and that they will be altered in the presence of stromal cells in coculture. To study the in vitro effects of DHEA on prostate cancer, we treated androgen receptor positive (LNCaP) prostate epithelial cells, growing alone or cocultured with prostate stromal cells, with various doses of DHEA, and then compared the effects of DHEA with those of T and DHT on expression of IGF-II, IGF-type I receptor (IGFIRb), IGF binding protein -2 (IGFBP-2), prostate specific antigen (PSA- an IGFBP-3 protease), and the androgen receptor (AR) by Western blotting analysis of cell lysates and conditioned media. PSA and IGF1Rb expression in LNCaP cells were modified by DHEA in a pattern similar to that induced by DHT and T. PSA secretion by LNCaP cells was increased further in the presence of prostate stromal cells in coculture. Additionally, the IGF1Rb expression in the stromal cell conditioned media was modified by coculture.
