Inhibitory Ah Receptor-Androgen Receptor Crosstalk in Prostate Cancer
Abstract
Treatment for prostate cancer depends on multiple factors including the stage of the tumor and expression of the androgen receptor (AR) . Endocrine therapy can be used for treatment of early stage androgen-responsive tumors, whereas chemotherapy for later stage androgen- nonresponsive tumors is problematic. We have investigated the aryl hydrocarbon receptor (AhR) as a potential target for treating prostate cancer using a new series of relatively non-toxic selective AhR modulators (SAhRMs) . Initial studies show that 22RV1, PC3 and LNCaP prostate cancer are Ah-responsive and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) induces CYP1A1-dependent activities in all three cell lines. Moreover, two SAhRMs, namely diindolylmethane (DIM) and 6-methyl-1,3,8-trichlorodibenzofuran (6-MCDF) inhibit growth of AR-positive 22RVl and AR-negative PC3 prostate cancer cells. In addition, AhR ligands inhibit dihydrotestosterone- induced upregulation of AR protein in 22RVl cells suggesting a possible mechanism for inhibitory AhR-AR crosstalk. The growth inhibitory effects of SAhRMs in PC3 cells suggests that AhR ligands also inhibit growth of androgen- nonresponsive cells. In addition, substituted DIMs inhibit growth of prostate cancer cells and modulate AR expression, and these are currently being investigated.
Document Details
- Document Type
- Technical Report
- Publication Date
- Feb 01, 2005
- Accession Number
- ADA436964
Entities
People
- Stephan H. Safe
Organizations
- Texas A&M University