Journal
ONCOGENE
Volume 19, Issue 15, Pages 1924-1932Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/sj.onc.1203511
Keywords
tea polyphenols; androgen receptor; theaflavins; prostate specific antigen; human glandular kallikrein; Sp1
Funding
- NCI NIH HHS [CA 70982] Funding Source: Medline
- NIDDK NIH HHS [DK 41995] Funding Source: Medline
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Androgens via their cognate receptor may be involved in the development and progression of prostate cancer. The aim of this study was to determine whether tea polyphenols have inhibitory effects on androgen action in an androgen-responsive, prostate cancer cell line, LNCaP, The tea polyphenol, EGCG, inhibited LNCaP cell growth and the expression of androgen regulated PSA and hK2 genes. Moreover, EGCG had a significant inhibitory effect on the androgenic inducibility of the PSA promoter. Immunoblotting detected a decrease in androgen receptor protein with treatments of the tea polyphenols EGCG, GCG and theaflavins, Northern blot analysis showed decreased levels of androgen receptor mRNA by EGCG, Transient transfections demonstrated that EGCG and theaflavins could repress the transcriptional activities of the androgen receptor promoter region. An Spl binding site in the androgen receptor gene promoter is an important regulatory component for its expression. This study suggests Spl is the target for the tea polyphenols because treatments of EGCG decreased the expression, DNA binding activity and transactivation activity of Spl protein. In conclusion, we have described a new property of tea polyphenols that inhibits androgen action by repressing the transcription of the androgen receptor gene.
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