Houghton J A, Adkins D A, Rahman A, Houghton P J
Department of Biochemical and Clinical Pharmacology, St. Jude Children's Research Hospital, Memphis, TN 38101.
Cancer Commun. 1991 Jul;3(7):225-31. doi: 10.3727/095535491820873236.
Recombinant human interferon-alpha 2a (rIFN-alpha 2a; 500 or 5,000 IU/mL) or [6RS] leucovorin ([6RS]LV; 1 microM) each potentiated the cytotoxic activity of 5-fluorouracil (FUra) by 2.6- to 3.2-fold during 72 hr exposures in two human colon adenocarcinoma cell lines (GC3/c1; VRC5/c1). When all three agents were combined, FUra cytotoxicity was further potentiated by 3.2- to 4.3-fold (total 10- to 14-fold). Potentiation of FUra cytotoxicity occurred at clinically achieveable concentrations of rIFN-alpha 2a and [6RS]LV. Effects were reversed by dThd (20 microM), although the activity of CB3717, a quinazoline-based, specific inhibitor of thymidylate synthase, was not potentiated by rIFN-alpha 2a. Data suggest the requirement of a 5-fluoropyrimidine for biochemical modulation and interaction at the level of thymidylate synthase or DNA.
