Chinese Red Yeast Rice inhibits tumor growth and downregulates expression of genes for androgen and cholesterol biosynthesis in human prostate cancer xenografts in SCID mice

Abstract

Statin use has been associated with a reduced risk of prostate cancer. Chinese Red Yeast Rice (RYR) is a traditional food spice containing a family of eight monacolins one of which (monacolin K) is identical to lovastatin. The effects of 5% RYR in the diet on the growth of androgen‐dependent (LNCaP) and androgen‐independent (LNCaP‐AR) prostate cancer xenografts in SCID mice over 8 wks was examined. The expression of genes regulating androgen biosynthesis and cholesterogenesis were determined by quantitative real time PCR. RYR inhibited both androgen‐dependent and ‐independent prostate tumor xenograft growth by 54% and 40 %, respectively (P<0.05). RYR downregulated HSD3B2, AKR1C3 and SRD5A1 genes for androgen synthesis more than two fold in both tumor xenografts (p<0.05). RYR also downregulated HMGCR and SREBP‐2 genes involved in de novo cholesterogenesis (P<0.05). RYR downregulated androgen receptor gene expression only in androgen‐independent xenografts (P<0.05). Androgens are known to increase the growth of prostate cancer xenografts but this is the first study to demonstrate that RYR inhibits tumor growth and gene expression for both cholesterol biosynthesis and androgen biosynthesis. These studies demonstrate one of several possible pathways of RYR action in prostate cancer and suggest potential biomarkers for human studies. Supported by the UCLA CNRU CA 42710 and DOD W81XWH‐07‐1‐0158.