Theaflavin-3,3'-digallate and penta-o-galloy1-B-D-glucose inhibit rat liver microsomal type 1 5a-reductase activity and the expression of androgen receptor in LNCaP prostate cancer cells

• Main Authors: Hung-Hsiao Lee, 李宏孝
• Other Authors: 林仁混
• Format: Others
• Language: en_US
• Published: 2003
• Online Access: http://ndltd.ncl.edu.tw/handle/80515265472629162351

碩士 === 國立臺灣大學 === 生物化學暨分子生物學研究所 === 91 === Androgens play a critical role in regulating the growth, differentiation and survival of epithelial cells in many androgen-responsive organs, such as prostate and skin. The enzyme steroid 5α-reductase (EC 1.3.99.5) catalyzes the NADPH-dependent reduction of the double bond of a variety of 3-oxo-∆4 steroids including the conversion of testosterone (T) to a more active androgen, dihydrotestosterone (DHT). DHT then binds to androgen receptors and functions in the nucleus to regulate specific gene expression. Androgens via their cognate receptor may be involved in the development and progression of benign prostate hyperplasia, prostate cancer, hirsutism, male pattern alopecia and acne. The aim of this study was to determine whether theaflavin-3,3’-digallate (TF3) and penta-O-galloyl-β-D-glucose (5GG) have inhibitory effects on androgen production and action. We found that TF3 and 5GG inhibit rat liver microsomal type 1 5α-reductase activities. 5GG and TF3 are both non-competitive inhibitors for T but they are competitive inhibitors for NADPH. Furthermore, TF3 and 5GG significantly reduced androgen-responsive LNCaP prostate cancer cell growth, suppressed expression of the androgen receptor (AR) and lowered androgen-induced prostate specific antigen (PSA) secretion and fatty acid synthase (FAS) protein expression. We also demonstrated that TF3 and 5GG decrease Sp1 protein level which is important for AR and FAS gene expression. In conclusion, our result suggests that TF3 and 5GG can attenuate the function of androgen and AR, which may be a useful chemoprevention or chemotherapeutic agent for prostate cancer.