Rhodacyanine Derivative Kills Resistant Cancers Figure 4. Brief exposure to YM-1 restores tamoxifen effect in resistant cell model. TR-MCF7 cells were treated with 4-OHT for 48 hours, YM-1 (or vehicle) for 4 hours followed by 44 hours of either 4-OHT or 95% EtOH, or YM-1 (or vehicle) for 48 hours. At 48 hours from initial treatment, MTT viability assays were performed. Viability values of each treatment as a % of 48 hours of 4-OHT treatment 6 SD (A). 2-Way ANOVA analysis comparing all YM-1 treatment groups (Gray squares- 4-hour YM-1then 4-OHT, open diamonds- 48 hour YM-1, black triangles- 4-hour YM-1 then 95% EtOH), revealed significance across concentrations (F(2,30) = 54.22, p,0.0001), and treatment strategy (F(4, 30) = 41.04, p,0.0001), but no significant interaction (F(8,30) = 1.83, p = 0.1107). * - indicates significant difference (p,0.05) of 4-hour YM-1 then 4-OHT from other two groups with exception of 10 mM treatments, significance as indicated (ns = p.0.05)(B). 1-way ANOVA of YM-1+4-OHT strategy revealing significance of 10 mM concentration (F(4,10) = 16.49, p = 0.0002)(C). Analysis of YM-1+95% EtOH, by 1-way ANOVA, revealed no significance across tested concentrations (F(4,10) = 3.435, p = 0.0516)(D). 48-hour YM-1 treatment showed significance differences between all concentrations and the 10 mM concentration, by 1-way ANOVA (F(4,10) = 12.32, p = 0.0007)(E). 1-way ANOVA analysis (F,(5,12) = 24.33, p,0.0001) comparing all 10 mM YM-1 treatments, 48-hour 4-OHT, and vehicle treatments revealed no significant difference between 48-hour 4-OHT and both 4-hour 10 mM YM-1+95% EtOH and 48-hour 10 mM YM-1 treatments; whereas the 48-hour 4-OHT and the 4-hour 10 mM YM-1+95% EtOH were significantly different from the 4-hour YM-1+4-OHT treatment (p,0.05)(F). doi:10.1371/journal.pone.0035566.g004 PLoS ONE | www.plosone.org 5 April 2012 | Volume 7 | Issue 4 | e35566