TY - JOUR
T1 - The effect of fluoropyrimidines with or without thymidine phosphorylase inhibitor on the expression of thymidine phosphorylase
AU - De Bruin, Michiel
AU - Van Capel, Toni
AU - Smid, Kees
AU - Fukushima, Masakazu
AU - Hoekman, Klaas
AU - Pinedo, Herbert M.
AU - Peters, Godefridus J.
N1 - Funding Information: This study was sponsored by the Spinoza award from NWO, received by Prof. Dr. H.M. Pinedo. We thank Dr. R. Honeywell for carefully reading the manuscript.
PY - 2004/5/3
Y1 - 2004/5/3
N2 - Thymidine phosphorylase (platelet-derived-endothelial-cell-growth-factor) catalyzes the reversible phosphorolysis of thymidine to thymine and 2-deoxyribose-1-phosphate, activates 5′-deoxy-5-fluorouridine (5′DFUR) and inactivates trifluorothymidine (TFT). The effect of 5′DFUR and TFT with or without a specific thymidine phosphorylase inhibitor (TPI) on thymidine phosphorylase mRNA, protein expression and activity was studied, in three human colon cancer cell lines, WiDR, HT29 and Lovo exposed for 72 h at IC50 concentrations. In Lovo cells TFT plus TPI only increased thymidine phosphorylase-protein expression 1.7-fold; 5′DFUR and TFT treatment increased thymidine phosphorylase mRNA levels 5- and 1.4-fold, respectively. In WiDR cells, 5′DFUR plus TPI significantly decreased thymidine phosphorylase-protein. TFT and TFT plus TPI increased thymidine phosphorylase-protein 2- and 3-fold, respectively. TPI and 5′DFUR decreased thymidine phosphorylase-mRNA levels significantly. In HT29 cells, 5′DFUR and 5′DFUR plus TPI decreased both thymidine phosphorylase-protein and thymidine phosphorylase-mRNA. In all cell lines 5′DFUR and TFT did not affect thymidine phosphorylase activity, but treatment with TPI (alone or in combination) eliminated thymidine phosphorylase activity. This demonstrated that regulation is drug and cell line dependent.
AB - Thymidine phosphorylase (platelet-derived-endothelial-cell-growth-factor) catalyzes the reversible phosphorolysis of thymidine to thymine and 2-deoxyribose-1-phosphate, activates 5′-deoxy-5-fluorouridine (5′DFUR) and inactivates trifluorothymidine (TFT). The effect of 5′DFUR and TFT with or without a specific thymidine phosphorylase inhibitor (TPI) on thymidine phosphorylase mRNA, protein expression and activity was studied, in three human colon cancer cell lines, WiDR, HT29 and Lovo exposed for 72 h at IC50 concentrations. In Lovo cells TFT plus TPI only increased thymidine phosphorylase-protein expression 1.7-fold; 5′DFUR and TFT treatment increased thymidine phosphorylase mRNA levels 5- and 1.4-fold, respectively. In WiDR cells, 5′DFUR plus TPI significantly decreased thymidine phosphorylase-protein. TFT and TFT plus TPI increased thymidine phosphorylase-protein 2- and 3-fold, respectively. TPI and 5′DFUR decreased thymidine phosphorylase-mRNA levels significantly. In HT29 cells, 5′DFUR and 5′DFUR plus TPI decreased both thymidine phosphorylase-protein and thymidine phosphorylase-mRNA. In all cell lines 5′DFUR and TFT did not affect thymidine phosphorylase activity, but treatment with TPI (alone or in combination) eliminated thymidine phosphorylase activity. This demonstrated that regulation is drug and cell line dependent.
KW - 5′-Deoxyfluorouridine
KW - Thymidine phosphorylase
KW - Thymidine phosphorylase inhibitor
KW - Trifluorothymidine
UR - http://www.scopus.com/inward/record.url?scp=2342566985&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/j.ejphar.2004.03.025
DO - https://doi.org/10.1016/j.ejphar.2004.03.025
M3 - Article
C2 - 15140625
SN - 0014-2999
VL - 491
SP - 93
EP - 99
JO - European journal of pharmacology
JF - European journal of pharmacology
IS - 2-3
ER -