Modulating testosterone stimulated prostate growth by phenethyl isothiocyanate via Sp1 and androgen receptor down-regulation

Prostate. 2007 Jun 1;67(8):863-70. doi: 10.1002/pros.20472.

Abstract

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.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Anticarcinogenic Agents / pharmacology*
  • Apoptosis / drug effects
  • Apoptosis / physiology*
  • Blotting, Western
  • Histocytochemistry
  • In Situ Nick-End Labeling
  • Isothiocyanates / pharmacology*
  • Male
  • Organ Size / drug effects
  • Prostate / drug effects*
  • Prostate / growth & development
  • Prostate / metabolism
  • Random Allocation
  • Rats
  • Rats, Wistar
  • Receptors, Androgen / metabolism
  • Sp1 Transcription Factor / metabolism
  • Testosterone / pharmacology*

Substances

  • Anticarcinogenic Agents
  • Isothiocyanates
  • Receptors, Androgen
  • Sp1 Transcription Factor
  • Testosterone
  • phenethyl isothiocyanate