A clinically achievable concentration of Ribavirin (10 μ M), which was not cytotoxic to primary CLL lymphocytes in culture, significantly sensitized 76% of the samples tested to FLU with the sensitization index (R) ranging from 1.25 to eightfold.
At 500 nM, the sensitization index of PZ-34 and PZ-38 are 8.7 and 14.3, respectively (Table 2).
On the other hand, the sensitization index of FTC at 500 nM is only 3.9 (Table 2).
At 500 nM, the sensitization index of PZ-39 is 0.04 whereas that of FTC at the same concentration is 0.26 (Fig. 3D and Table 2).
As shown in Fig. 3C, PZ-39 at 50 nM significantly reduced the IC50 of mitoxantrone with a sensitization index of 0.4 (Table 2).
At 50 nM, PZ-34 and PZ-38 significantly reduce the IC50 of mitoxantrone with a sensitization index of 1.6 and 2.2, respectively (Table 2).
In cell survival assay, PZ-39 at 500 nM was able to sensitize ABCG2-mediated mitoxantrone resistance with an index of 0.04 whereas FTC at the same concentration has a sensitization index of 0.26, ∼7-fold difference.
Indeed, the sensitization index for UNG−/− cells to raltitrexed was far smaller than the sensitization index for UNG−/− cell to pemetrexed, suggesting that UNG expression and activity has a greater role in pemetrexed versus raltitrexed response.
