Preferential induction of G1 arrest in androgen-responsive human prostate cancer cells by androgen receptor signaling antagonists DL3 and antiandrogen bicalutamide

Shan Lu, Zongqin Tan, Matthew Wortman, Shan Lu, Zhongyun Dong
Cancer Letters 2010 December 8, 298 (2): 250-7
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.

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