Stimulation of 5-fluorouracil metabolic activation by interferon-α in human colon carcinoma cells

Edward L. Schwartz, Mark Hoffman, Carolyn J. O'Connor, Scott Wadler

Research output: Contribution to journalArticle

123 Citations (Scopus)

Abstract

Interferon-α (IFNα) increases the cytotoxicity of 5-fluorouracil (FUra) in vitro, and the combination has clinical efficacy against advanced colorectal cancer. IFNα treatment of HT-29 colon carcinoma cells induced a greater than two-fold increase in the intracellular levels of the active metabolite of FUra, FdUMP. Using cell extracts from HT-29 cells and FUra as substrate, IFNα produced a 1.9- and 8.7-fold increase, respectively, in the activities of uridine phosphorylase and pyrimidine nucleoside phosphorylase (PyNP). Furthermore, the effect was selective for the conversion of FUra to FdUMP, as IFNα did not increase the cellular levels of FUTP, nor did it change the extent of incorporation of FUra into RNA (or DNA). IFNα also had no effect on thymidine kinase activity, the second step in the activation of FUra. Hence the effect of IFNα on PyNP activity is likely a critical biochemical event that modulates the cytotoxicity of FUra.

Original languageEnglish (US)
Pages (from-to)1232-1239
Number of pages8
JournalBiochemical and Biophysical Research Communications
Volume182
Issue number3
DOIs
StatePublished - Feb 14 1992

Fingerprint

Fluorouracil
Interferons
Colon
Chemical activation
Cells
Carcinoma
Pyrimidine Phosphorylases
Fluorodeoxyuridylate
Cytotoxicity
Uridine Phosphorylase
HT29 Cells
Thymidine Kinase
Metabolites
Metabolic Activation
Cell Extracts
Colorectal Neoplasms
RNA
DNA
Substrates

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

Stimulation of 5-fluorouracil metabolic activation by interferon-α in human colon carcinoma cells. / Schwartz, Edward L.; Hoffman, Mark; O'Connor, Carolyn J.; Wadler, Scott.

In: Biochemical and Biophysical Research Communications, Vol. 182, No. 3, 14.02.1992, p. 1232-1239.

Research output: Contribution to journalArticle

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