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Tea polyphenols down-regulate the expression of the androgen receptor in LNCaP prostate cancer cells
1Department of Urology, Mayo Graduate School, Mayo Foundation, Rochester, Minnesota, MN 55905, USA.
Abstract:
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 Sp1 binding site in the androgen receptor gene promoter is an important regulatory component for its expression. This study suggests Sp1 is the target for the tea polyphenols because treatments of EGCG decreased the expression, DNA binding activity and transactivation activity of Sp1 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.
Insights
Tea polyphenols, like EGCG, inhibit prostate cancer growth by blocking androgen receptor signaling. These compounds reduce androgen receptor expression and activity, offering a potential new strategy for prostate cancer treatment.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Androgen receptor signaling is crucial for prostate cancer development and progression.
- Prostate cancer cell lines like LNCaP are androgen-responsive, making them suitable models for studying androgen action.
Purpose of the Study:
- To investigate the inhibitory effects of tea polyphenols on androgen action in prostate cancer.
- To determine if specific tea polyphenols can modulate androgen receptor signaling pathways.
Main Methods:
- Cell growth assays using LNCaP cells treated with EGCG.
- Gene expression analysis (PSA, hK2, androgen receptor mRNA) via Northern blot.
- Western blot to assess androgen receptor protein levels.
- Reporter gene assays to evaluate promoter activity (PSA and androgen receptor promoters).
- Electrophoretic mobility shift assays (EMSA) and Western blot to assess Sp1 activity.
Main Results:
- Epigallocatechin gallate (EGCG) inhibited LNCaP cell proliferation and suppressed androgen-regulated genes (PSA, hK2).
- EGCG significantly reduced the inducibility of the PSA promoter by androgens.
- Tea polyphenols (EGCG, GCG, theaflavins) decreased androgen receptor protein and mRNA levels.
- EGCG and theaflavins repressed androgen receptor promoter activity, with EGCG targeting Sp1 activity.
Conclusions:
- Tea polyphenols inhibit androgen action by repressing androgen receptor gene transcription.
- The inhibitory effect of tea polyphenols involves the modulation of Sp1 transcription factor activity.
- These findings highlight a novel mechanism for tea polyphenols in potentially managing prostate cancer.