TY - JOUR
T1 - Suppression of Δ5-androstenediol-induced androgen receptor transactivation by selective steroids in human prostate cancer cells
AU - Chang, Hong Chiang
AU - Miyamoto, Hiroshi
AU - Marwah, Padma
AU - Lardy, Henry
AU - Yeh, Shuyuan
AU - Huang, Ko En
AU - Chang, Chawnshang
PY - 1999/9/28
Y1 - 1999/9/28
N2 - 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 anti-androgens, 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.
AB - 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 anti-androgens, 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.
UR - http://www.scopus.com/inward/record.url?scp=0033613201&partnerID=8YFLogxK
U2 - 10.1073/pnas.96.20.11173
DO - 10.1073/pnas.96.20.11173
M3 - 文章
C2 - 10500149
AN - SCOPUS:0033613201
SN - 0027-8424
VL - 96
SP - 11173
EP - 11177
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 20
ER -
