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

Access to Document

10.3727/095535491820873236

Cite this

@article{b9248fa06f3f4a9d8678b53bd52cd76e,

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)",

volume = "3",

pages = "225--231",

journal = "Oncology Research",

issn = "0965-0407",

publisher = "Cognizant Communication Corporation",

number = "7",

}

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.

UR - http://www.scopus.com/inward/record.url?scp=0025848306&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0025848306&partnerID=8YFLogxK

U2 - 10.3727/095535491820873236

DO - 10.3727/095535491820873236

M3 - Article

C2 - 1867955

AN - SCOPUS:0025848306

VL - 3

SP - 225

EP - 231

JO - Oncology Research

JF - Oncology Research

SN - 0965-0407

IS - 7

ER -

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

Abstract

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this