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Differences in metabolism of 5‐fluorouracil and 5‐fluorouridine and regulation by glucosamine in human colon cancer multicell tumor spheroids
Author(s) -
Chen TongBin,
Bajzer Zěljko,
Macura Slobodan,
VukPavlović Stanimir
Publication year - 1999
Publication title -
nmr in biomedicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.278
H-Index - 114
eISSN - 1099-1492
pISSN - 0952-3480
DOI - 10.1002/(sici)1099-1492(199905)12:3<157::aid-nbm551>3.0.co;2-i
Subject(s) - fluorouracil , metabolism , colorectal cancer , glucosamine , floxuridine , spheroid , cancer research , chemistry , cancer , medicine , biochemistry , biology , in vitro
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 19 F and 31 P 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 triphosphates in FUra‐treated MTS, and the magnitude of stimulation of fluoropyrimidine incorporation into macromolecules in FUrd‐treated MTS were not predicted. Copyright © 1999 John Wiley & Sons, Ltd.