Differences in metabolism of 5-fluorouracil and 5-fluorouridine and regulation by glucosamine in human colon cancer multicell tumor spheroids

Tong Bin Chen, Željko Bajzer, Slobodan I Macura, Stanimir Vuk-Pavlovic

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Glucosamine (GlcN) modulates fluoropyrimidine metabolism and enhances cytotoxicity of 5-fluorouridine (FUrd), but not of 5-fluorouracil (FUra), in human tumor models. To elucidate the underlying metabolic differences between FUra and FUrd, by the use of 19F and 31P NMR spectroscopy we studied these drugs in multicell tumor spheroids (MTS) formed by human colon carcinoma cells HT-29. This experimental system allowed detailed kinetic measurements of anabolic intracellular phosphates and fluorophosphates over periods of up to 2 days. Time-dependent NMR data were reduced and interpreted by the use of nonlinear compartmental models which yielded numerical values for the empirical rate constants characterizing mass transfer among the compartments. An analysis of these rate constants indicated qualitative and quantitative differences in the metabolism of FUra and FUrd and in the effects of GlcN on these drugs. The enhanced generation of FUDP-hexoses was a predicted effect of GlcN, but inhibited formation of fluorouridine diphosphates and fluorouridine diphosphates and fluorouridine triphosphates in FUra-treated MTS, and the magnitude of stimulation of fluoropyrimidine incorporation into macromolecules in FUrd-treated MTS were not predicted.

Original languageEnglish (US)
Pages (from-to)157-167
Number of pages11
JournalNMR in Biomedicine
Volume12
Issue number3
DOIs
StatePublished - May 1999

Fingerprint

Glucosamine
Metabolism
Fluorouracil
Colonic Neoplasms
Tumors
Diphosphates
fluorophosphate
Rate constants
Neoplasms
HT29 Cells
Nonlinear Dynamics
Hexoses
Cytotoxicity
Macromolecules
Pharmaceutical Preparations
Nuclear magnetic resonance spectroscopy
Colon
Magnetic Resonance Spectroscopy
Mass transfer
Phosphates

ASJC Scopus subject areas

  • Spectroscopy
  • Radiology Nuclear Medicine and imaging
  • Radiological and Ultrasound Technology
  • Biophysics

Cite this

Differences in metabolism of 5-fluorouracil and 5-fluorouridine and regulation by glucosamine in human colon cancer multicell tumor spheroids. / Chen, Tong Bin; Bajzer, Željko; Macura, Slobodan I; Vuk-Pavlovic, Stanimir.

In: NMR in Biomedicine, Vol. 12, No. 3, 05.1999, p. 157-167.

Research output: Contribution to journalArticle

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