11-Ketodihydrotestosterone (11-KDHT; 1-10 nM; 24 hours; LNCaP and VCaP cells) treatment induces significant cell proliferation.
11-Ketodihydrotestosterone (11-KDHT; 0.1-10 nM; 7-10 days; LNCaP and VCaP cells) treatment results in the significant upregulation of KLK3, TMPRSS2 and FKBP5 in both LNCaP and VCaP cells, with the exception of KLK3 at 1 nM in LNCaP cells.
In PNT2 cells, only 20% of 11β-hydroxyandrostenedione (11OHA4) and 11β-hydroxytestosterone (11OHT) are metabolised with the former yielding 11keto-androstenedione (11KA4), 11-Ketodihydrotestosterone (11-KDHT) and 11β-hydroxy-5α-androstanedione (11OH-5αDIONE) and the latter yielding 11OHA4, 11KT and 11-Ketodihydrotestosterone with downstream products <0.03 μM.
In prostate cancer tissue, C11-oxy C19 metabolites at significantly higher levels than the C19 steroids are detected, with unconjugated 11-Ketodihydrotestosterone, 11KT and 11OHA4 levels ranging between 13 and 37.5 ng/g. Analyses of total steroid levels in plasma show significant levels of 11OHA4 (≈230-440 nM), 11KT (≈250-390 nM) and 11-Ketodihydrotestosterone (≈19 nM).
Cell Proliferation Assay
Cell Line: |
LNCaP and VCaP cells |
Concentration: |
0.1 nM, 1 nM or 10 nM |
Incubation Time: |
7 days (LNCaP cells) or 10 days (VCaP cells) |
Result: |
Induced significant cell proliferation.
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RT-PCR
Cell Line: |
LNCaP and VCaP cells |
Concentration: |
1 nM, 10 nM |
Incubation Time: |
24 hours |
Result: |
Resulted in the significant upregulation of KLK3, TMPRSS2 and FKBP5 in both LNCaP (Fig 3) and VCaP (Fig 4) cells.
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