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. 2013 Jun 3;123(7):2948–2960. doi: 10.1172/JCI66398

Figure 2. Stereospecificity of EPI-001 on AR transcriptional activity.

Figure 2

(A) LNCaP cells were transfected with luciferase reporters and treated with 1 nM R1881 for 48 hours. Data represent percent of control (DMSO). **P < 0.01, #P < 0.001 vs. DMSO; §P < 0.05 vs. EPI-001. (B) AR NTD transactivation assay in LNCaP cells treated with indicated concentrations of EPI-001 stereoisomers prior to treatment with 50 μM forskolin or DMSO. (C) Inhibition of androgen-induced DNA synthesis in LNCaP cells by stereoisomers of EPI-001 (25 μM) or bicalutamide (10 μM) treated with 0.1 nM R1881 for 48 hours. Data represent percent S-phase cells staining positive for BrdU incorporation (bivariate flow cytometric) from a representative experiment. (D) Effects of EPI-002 on androgen-dependent proliferation of LNCaP cells treated with R1881 compared with PC3 cell viability. (E) Decrease of CRPC LNCaP tumor volume in castrated mice administered EPI-001 mixture and stereoisomers (i.v. 50 mg/kg body weight) every other day for a total of 7 doses. Bicalutamide (10 mg/kg body weight) was administered daily by oral gavage. (F) Comparison of tumor volume from treatment with single stereoisomers. (G) Percent change of tumor volume of individual animals treated with stereoisomers or bicalutamide. (H) Body weight change at day 14 versus day 0. (I) mRNA levels of full-length AR and androgen-regulated genes measured from the LNCaP xenografts. Intact, noncastrated control group (n = 3). Values were normalized to housekeeping gene RPL13A. Data are mean ± SD (A and B) or mean ± SEM (D–F, H, and I). *P < 0.05; **P < 0.01; #P < 0.001.