Synergistic effect of 5-fluorodeoxyuridine and quinazoline antifolates on murine leukemia self-cultured in vitro

• Autorzy: Balinska M. , Szablewska I. , Janiszewska D. , Brzezinska A. , Pawelczak K.
• Języki publikacji: EN

Abstrakty

EN

The effect of thymidylate synthase inhibitors, fluorodeoxyuridine (FdUrd) and its two sulphonamide derivatives was examined in the culture of murine leukemia cells -- 5178Y (parental subline) and its fluorodeoxyuridine resistant subline 5178Y/F. A synergistic effect of the antimetabolites on cell survival was observed on exposure of the culture of either line to a slightly inhibitory concentration of FdUrd (1 nM) in combination with 2-desamino-2-methyl-10-propargyl-5,8-dideaza-pteroylsulphogluta mate or 2-desamino-2-methyl-10-propargyl-5,8-dideaza-pteroylsulphoglyci ne. This effect was accompanied by a marked reduction, in both cell lines of intracellular concentration of 5,10-methylenetetrahydro-pteroyl-polyglutamate, although its concentration in the resistant subline was 3 times as high as in the parental line. The inhibitory effect of combined drugs on the cellular pool of folates in 5178Y line depended also on the sequence of drug addition, whereas in the FdUrd resistant line this sequence was without any effect. The results obtained strongly suggest that under certain conditions inhibition of thymidylate synthesis by antifolates is intensified by a prior use of FdUrd.

Słowa kluczowe

EN

5-fluorodeoxyuridine; leukemia; thymidylate synthase; quinazoline antifolate; growth inhibition; antifolate

• Wydawca: -
• Czasopismo: Acta Biochimica Polonica
• Rocznik: 1997
• Tom: 44
• Numer: 4
• Opis fizyczny: p.735-742,fig.

Twórcy

autor

Balinska M.

• Polish Academy of Sciences, L.Pasteura 3, 02-093 Warsaw, Poland

autor

Szablewska I.

autor

Janiszewska D.

autor

Brzezinska A.

autor

Pawelczak K.

Bibliografia

• 1. Myers, C.E. (1985) The pharmacology of the fluoropyrimidines. Pharmacol. Rev. 331, 1- 15.
• 2. Langeback, R.J., Danenberg, P.V. & Heidel­berger, C. (1972) Thymidylate synthase me­chanism of inhibition by 5-fluoro-2-deoxy- uridylate. Biochem. Biophys. Res. Comrnun. 48, 1565-1571.
• 3. Danenberg, P.V. & l/ockshin, A. (1982) Thymidylate synthase-substrate complex for­mation. Mol. Cell. Biochem. 43, 49-57.
• 4. Danenberg, P.V., Heidelberger, C., Mulkins, M. & Petterson, A.R. (1981)The incorporation of 5-fluoro-2'-deoxyuridine into DNA of ma­mmalian tumor cells. Biochem. Biophys. Res. Commun. 102, 654-658.
• 5. Cory, J.G., Berland, J.C. & Carter, G.C. (1979) Effect of fluorouracil on RNA metabolism of Novikoff hepatoma cells. Cancer Res. 39, 4905—4913.
• 6. Akazava, S., Kumai, R., Yoshida, K., Ayusawa, D., Shimizu, K. & Seno, T. (1986) The cytotoxicity of 5-fluorouracil is due to its incorporation into RNA not its inhibition of thymidylate sythase evidenced by the use of a mouse cell mutant deficient in thymidylate synthase. Jpn J. Cancer Res. 77, 620-624.
• 7. Jones, T.R., Calvert, AH., Jackman, A.L., Brown, S.J. & Ilarrap, K.R. (1981) A potent antitumor quinazoline inhibitor of thymidy­late synthase: Synthesis, biological properties and therapeutic results in mice. Eur. J. Can­cer 17, 11-19.
• 8. Pawełczak. K., Makowski, M., Kempny, M., Dzik, J.M., Balińska, M. & Rode, W. (1993) Sulphonamide antifolates inhibiting thymi­dylate synthesis, enzyme inhibition and cyto­toxicity. Adv. Exp. Med. Biol. 338, 625- 627.
• 9. Jacewicz, D., Kaczorowska, K., Szablewska, 1. & Balińska, M. (1995) Effect of antifolates on intracellular level of folates and folate en­zymes in 5178Y murine leukemia cells. J. Exp. Clin. Cancer Res. 14, 24-26.
• 10. Bretner, M., Kulikowski, T., Dzik, J.M., Balińska, M., Rode, W. & Shugar, D. (1993) 2-Thioderivativcs of dUrd and 5-fluoro dUrd and their 5'monophosphates, synthesis, in­teraction with tumour thymidylate synthase and in vitro antitumour activity. J. Med. Chem. 36, 3613-3617.
• 11. McGuire, J.J., Ilsieh, P., Coward, J.K. & Bertino, J.R. (1980) Enzymatic synthesis of folylpolyglutamates. Characterization of the reaction and its products. J. Biol. Chem. 255, 5776-5788.
• 12. Sikora, E., Krzyżanowski, L. & Rzeszotarska, B. (1989) A rapid, sensitive, nonradioactive assay for scrum y-glutamyl hydrolase using synthetic M4-aminobenzoyl)-,/-oligo(L-gluta- mic acids) as substrates. Pteridines 1, 175- 178.
• 13. Bradford, M. (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal. Biochem. 72, 248- 254.
• 14. Hryniuk, W.M., Fisher, G.A. & Bertino, J.R. (1969) S-phase cells of rapidly growing and resting populations. Differences in response to methotrexate. Mol. Pharmacol. 5,557-564.
• 15. Bunni, M., Doig, M.T., Donato. H., Kesaran, V. & Priest, D.G. (1988) Role of methyle- netetrahydrofolate depletion in methotr- exate-mediated intracellular thymidylate synthesis inhibition in cultured L1210. Can­cer Res. 48, 3398-3404.
• 16. Chou, T.C. & Talalay, P. (1984) Quantitative analysis of dose-effect relationship: The com­bined effects of multiple drugs or enzyme inhibitors. Adv. Enzyme Regul. 22, 27-55.
• 17. Sikora, E., Jackman, A.L., Newell, D.R. & Calvert, A.H. (1988) Formation and retention and biological activity of iV10-propargy 1-5,8- dideazafolic acid (CB3717) polyglutamates in L1210 cells in vitro. Biochem. Pharmacol. 37, 4047-4054.
• 18. Balińska, M. (1986) Synthesis and retention of methotrexate polyglutamates in Ehrlich ascites carcinoma cells. Drugs Exptl. Clin. Res. 12, 551-554.
• 19. Moran, R.G. (1989) Leucovorin enhancement of the effect of the fluoropyrimidines on thymidylate synthesis. Cancer 63, 3008- 1012.
• 20. Carreras, C.W. & Santi, D.V. (1995) The cata­lytic mechanism and structure of thymidylate synthase. Annu. Rev. Biochem. 64, 721-762.
• 21. Monfort, W.R., Perry, K.M., Fauman, E.B., Fiszcr-Moore, J.S., Maley, G.F., Hardy, L., Maley, F. & Stroud, R.M. (1990) Structure, multiple site binding and segmental accomo­dation in thymidylate synthase on binding dUMP and an antifolate. Biochemistry 29, 6964-6976.
• 22. Fiszer-Moore, J.S., Monfort, W.R. & Stroud, R.M. (1990) Pairwise specificity and sequen­tial binding in enzyme catalysis: Thymidylate synthase. Biochemistry 29, 6977-6986.
• 23. Perry, K.M., Carreras, C.W., Chang, L.C. & Santi, D.V. (1993) Structures of thymidylate synthase with C-terminal deletion. Role of the C-terminus in alignment of 2'deoxyuridine- 5'-monophosphate and 5,10-methylenetetra- hydrofolate. Biochemistry 32, 7116-7125.
• 24. Pogolotti, A., Dannenberg, P.V. & Santi, D.V. (1986) Kinetics and mechanism of interaction of 10-propargyl-5,8-dideazafolate with thymi­dylate synthase. J. Med. Chem. 29, 478-482.
• 25. Fernandes, D.J. & Cranford, S.K. (1986) Dis­sociation of thymidylate biosynthesis from DNA biosynthesis by 5-fluoro-2'-deoxyuridine and dideazaisofolic acid. Cancer Res. 46, 1741-1747.