Preferential induction of G1 arrest in androgen-responsive human prostate cancer cells by androgen receptor signaling antagonists DL3 and antiandrogen bicalutamide.
The purpose of this study was to further characterize cell growth-inhibitory effects of a recently identified androgen receptor (AR) signaling inhibitor 6-amino-2-[2-(4-tert-butyl-pnenoxy)-ethylsulfanyl]-1H-pyrimidin-4-one (DL3)(5) and antiandrogen bicalutamide (Bic). DL3 was more potent than Bic in induction of G1 arrest and reduction of G1-related cell cycle protein expression in AR-positive LNCaP cells. DL3, but not Bic, moderately inhibited growth of AR-negative PC-3 cells independent of G1 arrest. The data indicated that DL3 inhibit cell growth in both AR-dependent and -independent manners and is potentially a potent therapeutic agent for the management of advanced human prostate cancer.
Lu
Shan
S
Department of Internal Medicine, The University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA.
Tan
Zongqin
Z
Wortman
Matthew
M
Lu
Shan
S
Dong
Zhongyun
Z
D000726:Androgen Antagonists / Q000494:pharmacology*; D059002:Androgen Receptor Antagonists; D000728:Androgens / Q000494:pharmacology; D000813:Anilides / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D002453:Cell Cycle / Q000187:drug effects; D018797:Cell Cycle Proteins / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D056741:Cyclin D / Q000378:metabolism; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D016193:G1 Phase / Q000187:drug effects*; D006801:Humans; D008297:Male; D009570:Nitriles / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology; D011744:Pyrimidinones / Q000494:pharmacology*; D011944:Receptors, Androgen / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013440:Sulfides / Q000494:pharmacology*; D014105:Tosyl Compounds / Q000494:pharmacology*
C553685:6-amino-2-(2-(4-tert-butylphenoxy)ethylsulfanyl)-1H-pyrimidin-4-one; D000726:Androgen Antagonists; D059002:Androgen Receptor Antagonists; D000728:Androgens; D000813:Anilides; D018797:Cell Cycle Proteins; D056741:Cyclin D; D009570:Nitriles; D011744:Pyrimidinones; D011944:Receptors, Androgen; D013440:Sulfides; D014105:Tosyl Compounds; C053541:bicalutamide; D018844:Cyclin-Dependent Kinases