ERK Suppression in DU145 Cells Selected for AG2034 Resistance is Associated with Decreased ATP, GARFT Inactivation and Increased ERK Signaling

Background: Previously, we showed that AG2034, an inhibitor of glycinamide ribonucleotide formyltransferase (GARFT) in the pathway for de novo purine synthesis, is cytotoxic to different prostate cancer cell lines in the absence of inosine and hypoxanthine in the culture media. Therefore, we examined DU145 androgen-independent prostate cancer cells selected for drug resistance over a prolonged period of time, in the absence of media components (inosine and hypoxanthine) required for salvage purine synthesis and in the continuous presence of AG2034.