Effect of thalidomide on the TGFβ-1-mediated synthesis of testosterone from DHEA in prostate cancer.

141 Background: TGFβ-1 induces conversion of DHEA to testosterone in prostate cancer stromal cells. We hypothesized that thalidomide would inhibit TGFβ-1-mediated formation of testosterone from DHEA. Methods: We grew LAPC4 or LNCaP prostate cancer epithelial cells and 6S primary prostate stromal cells in mono-/co-culture with DHEA (100nM) and/or TGFβ-1 (40 or 100pM). Testosterone and PSA concentration in media were ascertained using ELISA and corrected for cell count using CCK8 (%DHEA controls). Results: TGFβ-1 and DHEA induced a dose-dependent increase in the formation of testosterone over controls (∼5-6 fold; P<0.0001). Thalidomide (100μM) inhibited the formation of testosterone in cocultured cells treated with DHEA and TGFβ-1 (40pM) by 35% (P=0.0008). The thalidomide analogues, CPS49 (10μM) and lenalidomide (10μM) also had activity; CPS49 inhibited testosterone synthesis by 54% (P=0.010) while lenalidomide reduced testosterone by 15% (P=0.011). However, only thalidomide and CPS49 decreased median PSA s...