[Show abstract][Hide abstract] ABSTRACT: Androgens and the androgen receptor (AR) play critical roles in the prostate development via mesenchymal-epithelial interactions. Smooth muscle cells (SMC), differentiated from mesenchyme, are one of the basic components of the prostate stroma. However, the roles of smooth muscle AR in prostate development are still obscure.
We established the smooth muscle selective AR knockout (SM-ARKO) mouse model using the Cre-loxP system, and confirmed the ARKO efficiency at RNA, DNA and protein levels. Then, we observed the prostate morphology changes, and determined the epithelial proliferation, apoptosis, and differentiation. We also knocked down the AR in a prostate smooth muscle cell line (PS-1) to confirm the in vivo findings and to probe the mechanism.
The AR was selectively and efficiently knocked out in the anterior prostates of SM-ARKO mouse. The SM-ARKO prostates have defects with loss of infolding structures, and decrease of epithelial proliferation, but with little change of apoptosis and differentiation. The mechanism studies showed that IGF-1 expression level decreased in the SM-ARKO prostates and AR-knockdown PS-1 cells. The decreased IGF-1 expression might contribute to the defective development of SM-ARKO prostates.
The AR in SMCs plays important roles in the prostate development via the regulation of IGF-1 signal.
[Show abstract][Hide abstract] ABSTRACT: To investigate the activity of RRR-alpha-tocopheryloxybutyric acid (TOB), an ether analog of RRR-alpha-tocopheryl succinate (VES), in prostate cancer cells.
VES and TOB were used to treat prostate cancer LNCaP, PC3, and 22Rv1 cells and primary-cultured prostate fibroblasts. The proliferation rates were determined by MTT assay, the cell viabilities were determined by trypan blue exclusion assay, and the cell deaths were evaluated by using Cell Death Detection ELISA kit. The protein expression levels were determined by Western blot analysis.
The MTT growth assay demonstrated that TOB could effectively suppress the proliferation of prostate cancer cells, but not normal prostate fibroblasts. Mechanism dissections revealed that TOB reduced cell viability and induced apoptosis in prostate cancer cells similar to VES. In addition, both TOB and VES suppressed prostate-specific antigen (PSA) at the transcriptional level leading to reduced PSA protein expression. Furthermore, vitamin D receptor (VDR) expression increased after the addition of TOB.
Our data suggests that the VES derivative, TOB, is effective in inhibiting prostate cancer cell proliferation, suggesting that TOB could be used for both chemopreventive and chemotherapeutic purposes in the future.
Full-text · Article · Feb 2007 · Asian Journal of Andrology