Interaction between 5-fluorouracil, [6RS]leucovorin, and recombinant human interferon-α2a in cultured colon adenocarcinoma cells

J. A. Houghton, D. A. Adkins, A. Rahman, P. J. Houghton

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Recombinant human interferon-α2a (rIFN-α2a; 500 or 5,000 IU/mL) or [6RS] leucovorin ([6RS]LV; 1 μM) 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/cl; VRC5/cl). 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 achievable concentrations of rIFN-α2a and [6RS]LV. Effects were reversed by dThd (20 μM), although the activity of CB3717, a quinazoline-based, specific inhibitor of thymidylate synthase, was not potentiated by rIFN-α2a. Data suggest the requirement of a 5-fluoropyrimidine for biochemical modulation and interaction at the level of thymidylate synthase or DNA.

Original languageEnglish (US)
Pages (from-to)225-231
Number of pages7
JournalCancer communications
Issue number7
Publication statusPublished - Jan 1 1991


ASJC Scopus subject areas

  • Cancer Research

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