The liver X receptor agonist T0901317 acts as androgen receptor antagonist in human prostate cancer cells.
T0901317 is a potent non-steroidal synthetic liver X receptor (LXR) agonist. T0901317 blocked androgenic stimulation of the proliferation of androgen-dependent LNCaP 104-S cells and androgenic suppression of the proliferation of androgen-independent LNCaP 104-R2 cells, inhibited the transcriptional activation of an androgen-dependent reporter gene by androgen, and suppressed gene and protein expression of prostate specific antigen (PSA), a target gene of androgen receptor (AR) without affecting gene and protein expression of AR. T0901317 also inhibited binding of a radiolabeled androgen to AR, but inhibition was much weaker compared to the effect of the antiandrogens, bicalutamide and hydroxyflutamide. The LXR agonist T0901317, therefore, acts as an antiandrogen in human prostate cancer cells.
Chuu
Chih-Pin
CP
The Ben May Department for Cancer Research, The University of Chicago, CIS W325F, 929 E. 57th Street, Chicago, IL 60637, USA.
Chen
Rou-Yu
RY
Hiipakka
Richard A
RA
Kokontis
John M
JM
Warner
Karen V
KV
Xiang
Jialing
J
Liao
Shutsung
S
D059002:Androgen Receptor Antagonists; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004268:DNA-Binding Proteins / Q000819:agonists*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D006845:Hydrocarbons, Fluorinated; D000071518:Liver X Receptors; D008297:Male; D057093:Orphan Nuclear Receptors; D011471:Prostatic Neoplasms / Q000378:metabolism*; D011944:Receptors, Androgen / Q000378:metabolism*; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists*; D013449:Sulfonamides / Q000008:administration & dosage*; D005466:Fluorocarbons; D000096926:Benzenesulfonamides
D059002:Androgen Receptor Antagonists; D020533:Angiogenesis Inhibitors; D004268:DNA-Binding Proteins; D006845:Hydrocarbons, Fluorinated; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; D011944:Receptors, Androgen; D018160:Receptors, Cytoplasmic and Nuclear; D013449:Sulfonamides; C423915:T0901317; D005466:Fluorocarbons; D000096926:Benzenesulfonamides