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

doi:10.3727/095535491820873236

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

Research output: Contribution to journal › Article › peer-review

32 Scopus citations

Abstract

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 language	English (US)
Pages (from-to)	225-231
Number of pages	7
Journal	Cancer communications
Volume	3
Issue number	7
DOIs	https://doi.org/10.3727/095535491820873236
State	Published - 1991
Externally published	Yes

ASJC Scopus subject areas

Cancer Research

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

abstract = "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.",

author = "Houghton, {J. A.} and Adkins, {D. A.} and A. Rahman and Houghton, {P. J.}",

year = "1991",

doi = "10.3727/095535491820873236",

language = "English (US)",

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

Abstract

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