Modulating testosterone stimulated prostate growth by phenethyl isothiocyanate via spi and androgen receptor down-regulation

BACKGROUND. The effects of phenethyl isothiocyanate (PEITC), present naturally in cruciferous vegetables, on androgen-influenced growth of the prostate such as benign hyperplasia, was investigated. METHODS. Rats dosed with cyproterone acetate and testosterone, were fed at the same time with either PEITC or vehicle control. The growth of the prostates was compared to untreated rats. RESULTS. While testosterone increased the prostate mass (30%) and hyperplastic seminiferous tubules as compared to the untreated rats, PEITC feeding decreased the prostate mass and hyperplasia to roughly the levels of untreated rats (P < 0.05). PEITC negated the testosterone-mediated enhancement of the androgen receptor (AR), via down-regulating transcription factor Sp1 expression and Sp1 binding complex formation. Cell cycle progression was attenuated with decreases of cyclins, Rb, and up-regulates p27. CONCLUSIONS. PEITC modulates the testosterone-influenced growth by repressing Sp1, thus down-regulating AR and proliferation. PEITC from cruciferous vegetables may represent a regulator for hormone-dependent growth of the prostate.