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 language | English (US) |
|---|---|
| Pages (from-to) | 157-167 |
| Number of pages | 11 |
| Journal | NMR in Biomedicine |
| Volume | 12 |
| Issue number | 3 |
| DOIs | |
| State | Published - May 1999 |
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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 journal › Article
}
TY - JOUR
T1 - Differences in metabolism of 5-fluorouracil and 5-fluorouridine and regulation by glucosamine in human colon cancer multicell tumor spheroids
AU - Chen, Tong Bin
AU - Bajzer, Željko
AU - Macura, Slobodan I
AU - Vuk-Pavlovic, Stanimir
PY - 1999/5
Y1 - 1999/5
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0032995848&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0032995848&partnerID=8YFLogxK
U2 - 10.1002/(SICI)1099-1492(199905)12:3<157::AID-NBM551>3.0.CO;2-I
DO - 10.1002/(SICI)1099-1492(199905)12:3<157::AID-NBM551>3.0.CO;2-I
M3 - Article
C2 - 10414950
AN - SCOPUS:0032995848
VL - 12
SP - 157
EP - 167
JO - NMR in Biomedicine
JF - NMR in Biomedicine
SN - 0952-3480
IS - 3
ER -