Trifluorothymidine exhibits potent antitumor activity via the induction of DNA double-strand breaks

Experimental and Therapeutic Medicine

Volumn 2, Issue 3, 2011, Pages 393-397

  Suzuki, Norihiko ^a   Nakagawa, Fumio ^a   Nukatsuka, Mamoru ^a   Fukushima, Masakazu ^a  

^a TAIHO PHARMACEUTICAL CO LTD   (Japan)

Author keywords

5 fluoro 2' deoxy uridine; 5 fluorouracil; DNA double strand break; Trifluorothymidine

Indexed keywords

ADENINE; ALDEHYDE; APURINIC ACID; ATM PROTEIN; ATR PROTEIN; BRCA2 PROTEIN; CAPECITABINE; CELL EXTRACT; CHECKPOINT KINASE 1; CHECKPOINT KINASE 2; DOUBLE STRANDED DNA; METHYL CPG BINDING PROTEIN; TAS 102; THYMINE DNA GLYCOSYLASE; TRIFLURIDINE; UNCLASSIFIED DRUG; URACIL DNA GLYCOSIDASE;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANTINEOPLASTIC ACTIVITY; APYRIMIDINIC SITE; ARTICLE; CONCENTRATION (PARAMETERS); CONTROLLED STUDY; DNA DAMAGE; DNA STRAND BREAKAGE; ENZYME LINKED IMMUNOSORBENT ASSAY; HUMAN; HUMAN CELL; IC 50; MOUSE; NONHUMAN; PROTEIN PHOSPHORYLATION; TUMOR XENOGRAFT; WESTERN BLOTTING;

EID: 79953286918     PISSN: 17920981     EISSN: 17921015     Source Type: Journal    
DOI: 10.3892/etm.2011.244     Document Type: Article

References (24)

1. Heidelberger C, Parsons DG and Remy DC: Syntheses of 5-trifluoromethyluracil and 5-trifluoromethyl-2'-deoxyuridine. J Med Chem 7: 1-5, 1964.
2. Bresnick E and Wiliams SS: Effects of 5-trifluoromethyldeoxy-uridine upon deoxythymidine kinase. Biochem Pharmacol 16: 503-507, 1967.
3. Reyers P and Heidelberger C: Fluorinated pyrimidines: XXVI. Mammalian thymidylate synthetase: its mechanism of action and inhibition by fluorinated nucleotides. Mol Pharmacol 1: 14-30, 1965.
4. Eckstein JW, Foster PG, Finer-Moore J, Wataya Y and Santi DV: Mechanism-based inhibition of thymidylate synthase by 5-(trifluoromethyl)-2'-deoxyuridine 5'-monophosphate. Biochemistry 3: 15086-15094, 1994.
5. Umeda M and Heidelberger C: Comparative studies of fluorinated pyrimidines with various cell lines. Cancer Res 28: 2529-2538, 1968.
6. Murakami Y, Kazuno H, Emura T, Tsujimoto H, Suzuki N and Fukushima M: Different mechanisms of acquired resistance to fluorinated pyrimidines in human colorectal cancer cells. Int J Oncol 17: 277-283, 2000.
7. Emura T, Nakagawa F, Fujioka A, Ohshimo H, Yokogawa T, Okabe H and Kitazato K: An optimal dosing schedule for a novel combination antimetabolite, TAS-102, based on its intracellular metabolism and its incorporation into DNA. Int J Mol Med 13: 249-255, 2004.
8. Emura T, Suzuki N, Yamaguchi M, Ohshimo H and Fukushima M: A novel combination antimetabolite, TAS-102, exhibits antitumor activity in FU-resistant human cancer cells through a mechanism involving FTD incorporation in DNA. Int J Oncol 25: 571-578, 2004.
9. Suzuki N, Emura T and Fukushima M: Mode of action of trifluoro-thymidine (TFT) against DNA replication and repair enzymes. Int J Oncol (In press).
10. Nakamura J, Walger VE, Upton PB, Chiang SY, Kow YW and Swenberg JA: Highly sensitive apurinic/apyrimidinic site assay can detect spontaneous and chemically induced depurination under physiological conditions. Cancer Res 58: 222-225, 1998.
11. Nishikawa T, Munshi A, Story MD, Ismail S, Stevens C, Chada S and Meyn RE: Adenoviral-mediated mda-7 expression suppresses DNA repair capacity and radiosensitizes non-small-cell lung cancer cells. Oncogene 16: 7125-7131, 2004.
12. Hartman KY and Heidelberger C: Studies on fluorinated pyrimidines: XIII. Inhibition of thymidylate synthase. J Biol Chem 236: 3006-3013, 1961.
13. Santi DV and McHenry CS: 5-Fluoro-2'-deoxyuridinylate: covalent complex with thymidylate synthase. Proc Natl Acad Sci USA 69: 1855-1857, 1972.
14. Glazer RI and Lloyd LS: Association of cell lethality with incorporation of 5-fluorouracil and 5-fluorouridine into nuclear RNA in human colon carcinoma cells in culture. Mol Pharmacol 21: 468-473, 1982.
15. Greenhalgh DA and Parish JH: Effect of 5-fluorouracil on cytotoxicity and RNA metabolism in human colonic carcinoma cells. Cancer Chemother Pharmacol 25: 37-44, 1989.
16. Rogers WI, Hartman AC, Palm PE, Okstein C and Kensler CJ: The fate of 5-trifluoromethyl-2'-deoxyuridine in monkeys, dogs, mice, and tumor-bearing mice. Cancer Res 29: 953-961, 1969.
17. Dexter DL, Wolberg WH, Ansfield FJ, Helson L and Heidelberger C: The clinical pharmacology of 5-trifluoromethyl-2'-deoxyuridine. Cancer Res 32: 247-53, 1972.
18. Suzuki N and Fukushima M: Simple and rapid enzymatic method for the synthesis of single-strand oligonucleotides containing trifluorothymidine. Nucleosides Nucleotides Nucleic Acids 29: 896-904, 2010.
19. Bijnsdorp IV, Kruyt FA, Gokoel S, Fukushima M and Peters GJ: Synergistic interaction between trifluorothymidine and docetaxel is sequence dependent. Cancer Sci 99: 2302-2308, 2008.
20. Backus HH, Pinedo HM, Wouters D, Kuiper CM, Jansen G, van Groeningen CJ and Peters GJ: Differences in the induction of DNA damage, cell cycle arrest, and cell death by 5-fluorouracil and antifolates. Oncol Res 12: 231-239, 2000.
21. Brown EJ and Baltimore D: Essential and dispensable roles of ATR in cell cycle arrest and genome maintenance. Genes Dev 17: 615-628, 2003.
22. Morrison C, Sonoda E, Takao N, Shinohara A, Yamamoto K and Takeda S: The controlling role of ATM in homologous recombinational repair of DNA damage. EMBO J 19: 463-471, 2000.
23. Beucher A, Birraux J, Tchouandong L, Barton O, Shibata A, Conrad S, Goodarzi AA, Krempler A, Jeggo PA and Löbrich M: ATM and Artemis promote homologous recombination of radiation-induced DNA double-strand breaks in G2. EMBO J 28: 3413-3427, 2009.
24. Branzei D and Foiani M: Regulation of DNA repair throughout the cell cycle. Nat Rev Mol Cell Biol 9: 297-308, 2008.