Figure 4

The DTIC inhibitory effect is overcome by hypoxanthine. A, Structure of hypoxanthine (HX) and 2-azahypoxanthine (2-AzaHX). B, Dose response curve of WM266-4 cell survival to DTIC in the absence (vehicle) or presence of 100 μM hypoxanthine (HX). Untreated cells were set as 100%. C, Graph showing the GI50 for DTIC of six mutBRAF melanoma cell lines treated as in B. The average GI50 for cells co-treated with HX (336.5 μM) was significantly higher than for vehicle-treated cells (22.89 μM), as determined by Student’s t test. **p = 0.0046. D, Quantification of cell survival of five mutRAS melanoma cell lines upon treatment with 300 μM DTIC in the absence (vehicle) or presence of 100 μM hypoxanthine (HX). E, Cell survival of 3 mutBRAF and 3 mutNRAS cell lines treated with 50 μM or 300 μM DTIC respectively in the absence (-) or presence of 100 μM Guanosine (GR) or 2′5′-GMP (GMP).