Growth of heterotopic LNCaP prostate cancer tumor in nude mice is not affected by dietary calcium.

BACKGROUND: We attempted to provide experimental evidence linking increased dietary calcium to progression of prostate cancer, as suggested by some epidemiological studies, using a heterotopic prostate cancer nude mice model. METHODS: Twenty heterotopic LNCaP prostate cancer tumor bearing nude mice were randomly assigned to one of the four groups: (I) high fat/low calcium diet, (II) high fat and high calcium diet, (III) high fat diet fortified with Vitamin D3, and (IV) high fat and high calcium diet fortified with Vitamin D3. In addition to weekly animal weights and tumor size measurements, the serum prostate specific antigen (PSA), 25-hydroxy Vitamin D3, calcium, phosphorus, total protein, albumin (to account for bound calcium) [1], and serum alkaline phosphatase (a measure of bone loss) [2] were determined at the termination of experiments. RESULTS: Although the serum calcium and 25-hydroxy Vitamin D3 were significantly higher in groups III and IV compared to groups I and II (P < 0.05), there was no significant difference between the tumor growth rates, final tumor weights (P = 0.9), and the serum PSA levels (P = 0.94) between the four groups. CONCLUSIONS: The results suggest that dietary calcium does not significantly affect the growth of heterotopic LNCaP prostate cancer in nude mice.

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 (SAMC), a phytoconstituent from garlic, on the expression of androgen-responsive biomarkers, prostate specific antigen (PSA), and prostate specific membrane antigen (PSMA), in human prostatic carcinoma cells (LNCaP). METHODS: Secretion of PSA was determined as well as the activity of PSMA measured as a function of its ability to hydrolyze poly-gamma-glutamated folate and N-acetylaspartylglutamate (NAAG). Folate hydrolase capacity was also determined in SAMC-treated cells grown in charcoal stripped fetal calf serum (CS-FCS). In addition, testosterone disappearance was measured from culture media of SAMC-treated LNCaP and PC-3 cells as well as from cell free lysates. RESULTS: PSA secretions were significantly decreased compared to control values 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 measured as either folate hydrolase or NAAG dipeptidase (NAALADase) activity increased in cells treated with SAMC. PSMA-folate hydrolase activity in SAMC-treated 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 rate of testosterone disappearance from culture media at 6 hr (P < 0.01) and at 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 PC-3 cells treated with SAMC. In lysates of SAMC-treated LNCaP cells, the rate 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 treatment. 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 part, by diminishing the trophic effects of testosterone, likely by converting it to metabolites less reactive toward androgen receptors.