Suppression of #ADELTA#~5-androstenediol-induced androgen receptor transactivation by selective steroids in hinnan prostate cancer cells

摘要

Our earlier report suggested that androst.5. ene-3#beta#,7#beta#-diol (#DELTA#~5-androstenediol or Adiol) is a natural hormone with androgenic activity and that two potent anti- androgens, hydroxyflutamide (Eulexin) and bicalutamide (Casodex), fail to block completely the Adiol-induced andro- gen receptor (AR) transactivation in prostate cancer cells. Here, we report the development of a reporter assay to screen several selective steroids with anti-Adiol activity. Among 22 derivatives/metabolites of dehydroepiandrosterone, we found 4 steroids [no. 4, 1,3,5(10)-estratriene-17#alpha#-ethyny1-3,17#beta#- diol;no. 6, 17#alpha#-ethynyl-androstene-diol; no. 8, 3p,17#beta#- dihydroxy-androst-5-ene-16-One, and no. 10, 3#beta#-methylcar- bonate-androst-5-ene-7,17-dione] that have no androgenic activity and could also block the Adiol-induced AR transac- tivation in prostate cancer PC3 cells. Interestingly, these compounds, in combination with hydroxyflutamide, furthcr suppressed the Adiol-induced AR transactivation. Reporter assays further showed that these four anti.Adiol steroids have relatively lower glucocorticoid, progesterone, and estrogenic activity. Together, these data suggest some selective steroids might have anti-Adiol activity, which may have potential clinical application in the battle against the androgen- dependent prostate cancer growth.