Figure 6.

Compound 8 and compound 19 sensitize ovarian and colon cancer cells to FK866 via NAPRT inhibition. (A–F) HCT116 and OVCAR-8 were plated in 96-well plates (2 × 10³ cells/well) and allowed to adhere overnight. The following day, culture media were replaced with new media containing the respective treatments (i.e., with or without FK866 at increasing concentrations from 1 to 100 nM and the putative NAPRT inhibitors, added at 100 μM final concentration), and the plates were then incubated for 72 h. Afterwards, the cells were imaged using light microscopy as in (C), and cell viability was determined using the sulforhodamine B assay. Data are mean ± SD of three experimental replicates. (G,H) The same experimental procedure was employed as in (A–F). Single concentrations of the NAPRT inhibitors (100 µM), 100 nM FK866, 10 µM NA, and 10 µM NAMN were added. Data are mean ± SD of 4 experimental replicates. One representative experiment is shown. *, p < 0.05; ***, p < 0.001; ****, p < 0.0001; $$$$, p < 0.0001. The * symbols refer to the statistical significance compared to the treatment with FK866 alone, whereas the $ symbols refer to the statistical significance compared to the combined treatment with FK866 and the NAPRT inhibitors.