Trilostane, an inhibitor of 3β-hydroxysteroid dehydrogenase, has an agonistic activity on androgen receptor in human prostate cancer cells.
The intracellular androgen metabolism and cell activity in prostate cancer cells with mutated (LNCaP-FGC) or wild-type (VCaP) androgen receptors in the presence of trilostane, an inhibitor of 3β-hydroxysteroid dehydrogenase, were examined. Trilostane suppressed the intracellular production of androstenedione, testosterone, and dihydrotestosterone from dehydroepiandrosterone in LNCaP-FGC cells. In both LNCaP-FGC and VCaP cell types, the prostate-specific antigen (PSA) levels in media were increased by trilostane alone in a concentration-dependent manner. Both cells pretreated with trilostane showed a dose-dependent decrease in PSA production with bicalutamide (P<0.001). Trilostane should be used with particular concern when treating prostate cancer.
Takizawa
Itsuhiro
I
Division of Urology, Department of Regenerative and Transplant Medicine, Graduate School of Medical and Dental Sciences, Niigata University, Asahimachi 1, Niigata 951-8510, Japan.
Nishiyama
Tsutomu
T
Hara
Noboru
N
Hoshii
Tatsuhiko
T
Ishizaki
Fumio
F
Miyashiro
Yoshimichi
Y
Takahashi
Kota
K
D015096:3-Hydroxysteroid Dehydrogenases / Q000037:antagonists & inhibitors*; D000728:Androgens / Q000096:biosynthesis; D045744:Cell Line, Tumor; D002853:Chromatography, Liquid; D003687:Dehydroepiandrosterone / Q000378:metabolism; D013196:Dihydrotestosterone / Q000031:analogs & derivatives* / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D008297:Male; D013058:Mass Spectrometry; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D011944:Receptors, Androgen / Q000378:metabolism; D013739:Testosterone / Q000378:metabolism
D000728:Androgens; D004791:Enzyme Inhibitors; D011944:Receptors, Androgen; D013196:Dihydrotestosterone; D013739:Testosterone; D003687:Dehydroepiandrosterone; D015096:3-Hydroxysteroid Dehydrogenases; C009954:trilostane