pyrimidinones and 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.

Topics: Androgen Antagonists; Androgen Receptor Antagonists; Androgens; Anilides; Apoptosis; Blotting, Western; Cell Cycle; Cell Cycle Proteins; Cell Line, Tumor; Cell Proliferation; Cyclin D; Cyclin-Dependent Kinases; Dose-Response Relationship, Drug; G1 Phase; Humans; Male; Nitriles; Phosphorylation; Prostatic Neoplasms; Pyrimidinones; Receptors, Androgen; Signal Transduction; Sulfides; Tosyl Compounds