Chemoprevention of MNU and Testosterone induced prostate carcinogenesis by Calcitriol (vitamin D3) in adult male albino Wistar rats

Abstract

Background Calcitriol is a steroid hormone, inhibits the proliferation and promotes the differentiation of human prostate cancer cells. Calcitriol markedly inhibits the invasiveness of human prostate cancer cells in vitro. These properties support the use of calcitriol as differentiation therapy in prostate cancer. Chemopreventive role of calcitriol on prostate cancer remains unknown. Prostatic intraepithelial neoplasia (PIN) is the most common precancerous state and represents the major target for chemoprevention of prostate cancer.Methods Prostate cancer was induced in Wistar rats using MNU+T (N-Methyl nitroso urea + Testosterone). Calcitriol (0.5 μg/kg body weight) was administered weekly thrice as i.p. injection simultaneously to MNU+T treated rats. The control group received vehicle alone. After 16 weeks of experimental period ventral and dorsolateral lobes were removed for histopathological evaluation and serum prostatic acid phosphatase (PAcP) was determined.Results MNU+T treated rats showed hyperplasia, dysplasia and PIN (70%, 60% and 30%) changes in dorsolateral prostate and ventral prostate 60% 50% 30%, respectively. Where as MNU+T along with calcitriol treated rats, the incidence of hyperplasia, dysplasia and PIN in the ventral was 10% each and in dorsolateral it was 20%, 10% and 10%, respectively. Hyperplasia, dysplasia and PIN were less common in these rats. Serum PAcP significantly increases in MNU+T treated rats, whereas decreased in the calcitriol treated rats. The results of this study suggests that calcitriol may have chemopreventive activity in rat prostate carcinogenesis.Interpretation During the treatment with calcitriol on MNU+T induced prostate carcinogenesis, calcitriol might be capable of inhibiting the initiation of prostate cancer. Hence, calcitriol may have useful for the prevention of prostate cancer.