Open AccessSuppression of Δ 5 -androstenediol-induced androgen receptor transactivation by selective steroids in human prostate cancer cells
Author(s) -
Hong Chang,
Hiroshi Miyamoto,
Padma Marwah,
Henry A. Lardy,
Shuyuan Yeh,
Kuo Yuan Huang,
Chawnshang Chang
Publication year - 1999
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.96.20.11173
Subject(s) - androstenediol , transactivation , prostate cancer , androgen receptor , dihydrotestosterone , endocrinology , androgen , bicalutamide , medicine , chemistry , biology , dehydroepiandrosterone , hormone , cancer , biochemistry , transcription factor , gene
Our earlier report suggested that androst-5-ene-3β,7β-diol (Δ5 -androstenediol or Adiol) is a natural hormone with androgenic activity and that two potent antiandrogens, hydroxyflutamide (Eulexin) and bicalutamide (Casodex), fail to block completely the Adiol-induced androgen 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-17α-ethynyl-3,17β-diol; no. 6, 17α-ethynyl-androstene-diol; no. 8, 3β,17β-dihydroxy-androst-5-ene-16-one; and no. 10, 3β-methylcarbonate-androst-5-ene-7,17-dione] that have no androgenic activity and could also block the Adiol-induced AR transactivation in prostate cancer PC-3 cells. Interestingly, these compounds, in combination with hydroxyflutamide, further 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.