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Drug Combinations Evoke Collateral Sensitivity against ABCG2 TABLE 5 Effect of gramicidin or ouabain on relative resistance and reversal of resistance of ABCG2-expressing MCF-7/FLV1 and parental cells Compound Curcumin alone Gramicidin alone Gramicidin 2 M curcumin Gramicidin 2 M curcumin 10 M FTC Ouabain alone Ouabain 2 M curcumin Ouabain 2 M curcumin 10 M FTC IC50 MCF-7 control 7.3 0.5 M 190 20 nM 5011nM 4913nM 14 2 nM 14 1 nM 15 3 nM MCF-7/FLV1 5.4 0.5 M 850115nM 114nM 5112nM 152nM 62nM 163nM p value of IC50 from MCF-7/FLV1 cells relative to IC50 from MCF-7 cellsa 0.12 4E-3 0.03 0.85 0.74 0.02 0.70 Relative resistanceb 1.4 0.2-fold 4.5 0.8-fold 0.2 0.1-fold 1.0 0.1-fold 1.1 0.2-fold 0.4 0.1-fold 1.1 0.3-fold Reversal of resistancec 23 9-fold 4.5 1.7-fold 2.8 1.0-fold 1 0.3-fold a To determine p values, we used a two-tailed Student’s t test based on log(IC50) values. We considered p values 0.05 as statistically significant. b Expressed as the ratio of the IC50 value of ABCG2-expressing cells to that of the control cells. c Expressed as the ratio of the relative resistance value of ABCG2-expressing cells in the absence of the second compound to the relative resistance in its presence. FIGURE 11. Cell viability of MCF-7 and MCF-7/FLV1 cells as a function of increasing gA or ouabain concentrations and effect of curcumin, gA, and ouabain on the RMP of MCF-7 and MCF-7/FLV1 cells. A, sensitivity of MCF-7 cells (black) and MCF-7/FLV1 cells (red) to gA in the absence (solid curves) or presence (dashed curves) of 2 M curcumin. B, sensitivity of MCF-7 cells (black) and MCF-7/FLV1 cells (red) to ouabain in the absence (solid curves) or presence (dashed curves) of 2 M curcumin. C and D, cell viability of MCF-7 cells (black) and MCF-7/FLV1 cells (red) exposed to increasing doses of gA (C) or ouabain (D) in the presence of 2 M curcumin (cur) in the absence (dashed curves) or presence (solid curves) of 10 M FTC (see Table 5 for a statistical analysis of differences in IC50 values). E, effect of curcumin (cur), gA, and ouabain (oua) on the RMP of MCF-7 cells (black bars) and MCF-7/FLV1 cells (white bars). Cells were incubated under various conditions as indicated. The bars labeled with RMP represent the control without addition of compound(s). FTC was used at a concentration of 10 M. Triple asterisks indicate a difference compared with the control (RMP) with a p value 0.001. The values in brackets indicate the numbers of measurements. 31408 JOURNAL OF BIOLOGICAL CHEMISTRY VOLUME 289 • NUMBER 45 • NOVEMBER 7, 2014PDF Image | Curcumin with Either Gramicidin or Ouabain
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