Intracellular thymidylate synthase inhibition by trifluorothymidine in FM3A cells.
Article Details
- CitationCopy to clipboard
Temmink OH, Comijn EM, Fukushima M, Peters GJ
Intracellular thymidylate synthase inhibition by trifluorothymidine in FM3A cells.
Nucleosides Nucleotides Nucleic Acids. 2004 Oct;23(8-9):1491-4.
- PubMed ID
- 15571283 [ View in PubMed]
- Abstract
Trifluorothymidine (TFT) can be phosphorylated by thymidine kinase (TK) to TFTMP which can inhibit thymidylate synthase (TS), resulting in depletion of thymidine nucleotides. TFT can be degraded by thymidine phosphorylase (TP) which can be inhibited by thymidine phosphorylase inhibitor (TPI). Using the TS in situ Inhibition Assay (TSIA) FM3A breast cancer cells were exposed 4 h or 24 h to TFT and 5-Fluorouracil (5FU). TS activity reduced to 9% (0.1 microM TFT) and 58% (1 microM 5FU) after 4 h exposure and to 6% (TFT) and 21% (5FU) after 24 h exposure. TPI did not affect TS inhibition by TFT. FM3A cells lacking TK or TS activity (FM3A/TK-) were far less sensitive to TFT compared to FM3A cells. CONCLUSION: TFT can be taken up and activated very rapidly by FM3A cancer cells, probably due to favourable TK enzyme properties, and TPI did not influence this.
DrugBank Data that Cites this Article
- Drug Targets
Drug Target Kind Organism Pharmacological Action Actions Trifluridine Thymidylate synthase Protein Humans YesInhibitorDetails - Drug Enzymes
Drug Enzyme Kind Organism Pharmacological Action Actions Trifluridine Thymidine kinase, cytosolic Protein Humans UnknownSubstrateDetails Trifluridine Thymidine phosphorylase Protein Humans UnknownSubstrateDetails