Figure 1

(A) Chemical structures of RAMBA, VN/66-1 and HDAC inhibitor, MS-275. (B) Dose–response curve of VN/66-1 alone and the combination of VN/66-1 and MS-275 (simultaneous treatment) in PC-3 cells. ▪ denotes various concentrations of VN/66-1 alone; ▴ denotes VN/66-1 at various concentrations plus 0.1 μ M of MS-275; • shows the effect of 0.1 μ M MS-275 alone. ***P<0.005; **P<0.01; *P<0.05 (t-test). (C) The effect of AGN193109 (abbreviated AGN), a pan-RAR antagonist on cell viability (simultaneous treatment). PC-3 cells were treated with 1 μ M VN/66-1 and/or 0.1 μ M MS-275, and 0.1 μ M AGN193109. ***P<0.0001 (t-test). Data are mean (±s.e.) of at least three independent experiments (B and C). (D) Isobologram analysis of PC-3 cell growth inhibition by VN/66-1 and MS-275 simultaneously and sequentially. The IC75 values of each drug are plotted on the axes; the solid line represents the additive effect, while the points represent the concentrations of each compound resulting in 75% growth inhibition. Arrow indicates sequence of treatment.