Modulating testosterone stimulated prostate growth by phenethyl isothiocyanate via Sp1 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.
Beklemisheva
Anastasia A
AA
Department of Medicine, New York Medical College, Valhalla, New York 10595, USA.
Feng
Jingyang
J
Yeh
Yunshin Albert
YA
Wang
L G
LG
Chiao
J W
JW
D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D015153:Blotting, Western; D006651:Histocytochemistry; D020287:In Situ Nick-End Labeling; D017879:Isothiocyanates / Q000494:pharmacology*; D008297:Male; D009929:Organ Size / Q000187:drug effects; D011467:Prostate / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D011944:Receptors, Androgen / Q000378:metabolism; D016329:Sp1 Transcription Factor / Q000378:metabolism; D013739:Testosterone / Q000494:pharmacology*
D016588:Anticarcinogenic Agents; D017879:Isothiocyanates; D011944:Receptors, Androgen; D016329:Sp1 Transcription Factor; D013739:Testosterone; C058305:phenethyl isothiocyanate