TY - JOUR
T1 - Interaction between 5-fluorouracil, [6RS]leucovorin, and recombinant human interferon-α2a in cultured colon adenocarcinoma cells
AU - Houghton, J. A.
AU - Adkins, D. A.
AU - Rahman, A.
AU - Houghton, P. J.
PY - 1991
Y1 - 1991
N2 - 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.
AB - 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.
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U2 - 10.3727/095535491820873236
DO - 10.3727/095535491820873236
M3 - Article
C2 - 1867955
AN - SCOPUS:0025848306
SN - 0955-3541
VL - 3
SP - 225
EP - 231
JO - Cancer communications
JF - Cancer communications
IS - 7
ER -