Alterations of prostate biomarker expression and testosterone utilization in human LNCaP prostatic carcinoma cells by garlic-derived S-allylmercaptocysteine

BACKGROUND. This study determined the effects of S-allylmercaptocysteine (S AMC), a phytoconstituent from garlic, on the expression of androgen-respons ive biomarkers, prostate specific antigen (PSA), and prostate specific memb rane antigen (PSMA), in human prostatic carcinoma cells (LNCaP). METHODS. Secretion of PSA was determined as well as the activity of PSMA me asured as a function of its ability to hydrolyze poly-gamma -glutamated fol ate and N-acetylaspartylglutamate (NAAG). Folate hydrolase capacity was als o determined in SAMC-treated cells grown in charcoal stripped fetal calf se rum (CS-FCS). In addition, testosterone disappearance was measured from cul ture media of SAMC-treated LNCaP and PC-3 cells as well as from cell free l ysates. RESULTS. PSA secretions were significantly decreased compared to control va lues at. 1 day (8.4 +/- 2.6 vs. 18.9 +/- 1.7, P < 0.01), 4 days (18.9 +/- 5 .3 vs. 73.8 +/- 4.4, P < 0.001), and 6 days (35.6 +/- 2.1 vs. 96.5 +/- 17.9 ng/10(5) cells, P < 0.01; mean +/- SD). By contrast, PSMA activity measure d as either folate hydrolase or NAAG dipeptidase (NAALADase) activity incre ased in cells treated with SAMC. PSMA-folate hydrolase activity in SAMC-tre ated cells grown in CS-FCS increased beyond that observed in cells grown in CS-FCS alone. Pre-exposure of LNCaP cells to SAMC resulted in enhanced rat e of testosterone disappearance from culture media at 6 hr (P < 0.01) and a t 48 hr (P < 0.001) compared to media from cells not previously exposed to SAMC. Results similar to these were also observed in androgen-independent P C-3 cells treated with SAMC. In lysates of SAMC-treated LNCaP cells, the ra te of testosterone catabolism was twice that from phosphate buffered saline (PBS)-treated cells. SAMC-treated LNCaP cells grown in media supplemented with testosterone temporarily exhibited enhanced growth over a 2 day period but cell numbers declined later to levels similar to those of SAMC treatme nt. CONCLUSIONS. These results show that SAMC exhibits differential effects on recognized biomarkers for LNCaP cells similar to those produced by androgen deprivation and strongly suggests that this effect may be mediated, in par t, by diminishing the trophic effects of testosterone, likely by converting it to metabolites less reactive toward androgen receptors. (C) 2000 Wiley- Liss, Inc.