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 androgennon responsive tumors is problematic. We 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 showed that 22RV1, PC3 and LNCaP prostate cancer are Ah-responsive. Two SAhRMs, namely diindolylmethane (DIM) and 6-methyl-1,3,8- trichlorodibenzofuran (6-MCDF), inhibited growth of AR-positive 22RV1 and ARnegative PC3 cells. AhR ligands inhibited dihydrotestosterone-induced upregulation of AR protein in 22RV1 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, 2006
- Accession Number
- ADA460286
Entities
People
- Stephen Safe
Organizations
- Texas A&M University