Cellular Resistance to Antifolates

항엽산제에 대한 세포의 저항성 기작

  • Published : 1993.12.01

Abstract

One of the major problems of cancer chemotheraphy is the development of drug resistance in tumors, resulting in reduced responsiveness to subsequent treatments. The folate antagonists are being used to treat such diverse illnesses as cancer, leukemia, psoriasis, rheumatoid arthritis, etc. Previous studies have established that resistance to antifolates may occur in mammalian tumor cells by one or more of five mechanisms ; (a) an increase in the levels of the target enzyme, generally as a consequence of gene amplification ; (b) an alteration in the target enzyme, leading to an enzyme with a decreased binding affinity for the drug ; (c) a decrease in the uptake of the drug into the cells ; (d) increased extrusion of drugs out of cells ; (e) impaired ability to polyglutamylate the parent drug which is capable of being intracellularly metabolized to longer chain length.

Keywords

References

  1. Ann. Rev. Nutr. v.5 Vitamin $B_{12}$-folate interrelationship Shane,B.;Stokstad,E.L.R.
  2. Vitamins and Hormones v.45 Folypolyglutamate synthesis and role in the regulation of one-carbon metabolism Shane,B.
  3. Science v.257 Agencies split on nutrition advice Palca,J.
  4. FASEB J. v.4 Dihydrofolate reductase as a therapeutic target Schweitzer,B.I.;Dicker,A.P.;Bertino,J.R.
  5. Am. J. Clin. Nutr. v.50 Folic acid safety and toxicity : A brief review Butterworth,C.E.;Tamura,T.
  6. Cancer Res. v.49 Inherent resistance of human squamous carcinoma cell lines to methotrexate as a result of decreased polyglutamylation of this drug Pizzorno,G.;Chang,Y.M.;McGuire,J.J.;Bertino,J.R.
  7. Cancer Res. v.48 Role of methotrexate polyglutamates in methotrexate and sequential methotrexate-5-fluorouracil-mediated cell kill McGuire,J.J.;Mini,E.;Hsieh,P.;Bertino,J.R.
  8. Proceedings of the sixth international conference on pteridines and related biogenic amines and folates Advances in antifolate development Kisliuk,P.L.;Blau,N.(ed.);Curtius,H.C.(ed.);Levine,R.(ed.);Yin,J.(ed.)
  9. Cancer Res. v.50 Activity of the thymidylate synthase inhibitor 2-dsamino-N10-propargyl-5, 8-dideazafolic acid and related compounds in murine(L1210) and human(W1L2) systems in vitro and in L1210 in vivo Jackman,L.A.;Taylor,G.A.;O'Conner,B.M.;Bishop,J.A.;Moran,R.G.;Calvert,A.H.
  10. Biochem. Pharmacol. v.41 Studies on the mechanism of antitumor action of 2-des-amino-2-methyi-5,8-dideazaisofolic acid Hagan,R.L.;Duch,D.S.;Smith,G.K.;Hanlon,M.H.;Shane,B.;Freisheim,J.H.;Hynes,J.B.
  11. Cancer Res. v.51 ICID 1964, a quinazoline antifolate thymidylate synthase inhibitor that is a potent inhibitor of L1210 tumor cell growth in vitro and in vivo : A new agent for clinical study Jackman,A.L.;Taylor,G.A.;Gibson,W.;Kimbell,R.;Brown,M.;Calvert,A.H.;Judson,I.R.;Hughes,L.R.
  12. J. Med. Chem. v.33 Synthesis and biological activity of an acyclic analogue of 5,6,7,8-tetrahydrofolic acid, N-[4-[[3-(2,4-diamino-1,6-dihydro-6-oxo-5-pyrimidinyl)propyl]amino]-benzoyi]-L-glutamic acid Kelly,J.L.;McLean,E.W.;Cohn,N.K.;Edeistein,M.K.;Duke,D.S.;Smith,G.K.;Hanlon,M.H.;Ferone,R.
  13. Cancer Res. v.49 Inhibition of glycinamide ribonucleotide formyltransferase and other folate enzymes by homofolate polyglutamates in human lymphoma and murine leukimia cell extracts Thorndike,J.;Gaumont,Y.;Kisliuk,R.L.;Sirotnak,F.M.;Murthy,B.R.;Nair,M.G.;Piper,J.R.
  14. J. Biol. Chem. v.264 A new folate antimetabolites, 5, 10-dideaza-5, 6, 7, 8-tetrahydrofolate is a potent inhibitor of de novo purine synthesis Beardsley,G.P.;Moroson,B.A.;Taylor,E.C.;Moran,R.G.
  15. Cancer Res v.50 In vivo and in vitro metabolism of 5-deazaacy-clotetrahydrofolate, an acyclic tetrahydrofolate analogue Hanlon,M.H.;Ferone,R.;Mullin,R.J.;Keith,B.R.
  16. Cancer Res. v.49 Induction of Hl-60 leukemia cell differentiation by the novel antifolate 5, 10-dideazatetrahydrofolic acid Sokoloski,J.A.;Beardsley,G.P.;Sartorelli,A.C.
  17. Method in Enzymology v.151 Amplification of genes in somatic mammalian cells Schimke,R.T.;Roos,D.S.;Brown,P.C.
  18. Cancer Res. v.48 Role of folypolyglutamate synthetase in the regulation of methotrexate polyglutamate formation in H35 hepatoma cells Johnson,T.B.;Nair,M.G.;Galivan,J.
  19. Cancer Res. v.48 Impaired polyglutamylation of methotrexate as a cause of resistance in CCRF-CEM cells after short-term, high-dose treatment with this drug Pizzorno,G.;Mini,E.;Coronello,M.;McGuire,J.J.;Moroson,B.A.;Cashmore,A.R.;Dreyer,R.N.;Lin,J.;Mazzei,T.;Periti,P.;Bertino,J.R.
  20. J. Biol. Chem. v.268 Regulation of folate and one carbon metabolism in mammalian cells Kim,J.;Lowe,K.E.;Shane,B.
  21. Ph. D. dissertation , Dept. of Nutritional Sciences, University of California at Berkeley Cytotoxicity and metabolism of antifolates Kim,J.
  22. J. Biol. Chem. v.265 Indentification and characterization of a mutation in the dihydrofolate reductase gene from the methotrexate-resistant Chinese hamster ovary cell line $pro^{-3}\;Mtx^{RMt}$ Dicker,A.P.;Volkenandt,M.;Schweitzer,B.L.;Banerjee,D.;Bertino,J.R.
  23. J. Biol. Chem. v.263 Gene amplification in cultured cells Schimke,R.T.
  24. Cell v.57 Recent progress in understanding of mammalian DNA amplification Stark,G.R.;Debatisse,E.G.;Wahl,G.M.
  25. J. Biol. Chem. Role of folylpolyglutamate synthease in the metabolism and cytotoxicity of 5-deazaacyclotetrahydrofolate, an anti-purine drug Kim,J.;Shane,B.
  26. Proc. Natl. Acad. Sci. USA v.78 Methotrexate-resistant Chinese hamster ovary cells have amplified a 135-kilobase-pair region that includes the dihydrofolate reductase gene Milbrandt,J.D.;Heintz,N.H.;White,W.C.;Rothman,S.M.;Hamlin,J.L.
  27. Cancer Res. v.45 Cytotoxic effects of folate antagonists against methotrexate-resistant human leukemia lymphoblast CCRF-CEM cell lines Mini,E.;Moroson,B.A.;Franco,C.T.;Bertino,J.R.
  28. J. Med. Chem. v.32 Inhibition of mammalian folylpolyglutamate synthetase and human dihydrofolate reductase by 5,8-dideaza analogues of folic acid and aminopterin bearing a terminal L-ornithine Patil,S.A.;Shane,B.;Freisheim,J.H.;Singh,S.K.;Hynes,J.B.
  29. Proc. Natl. Acad. Sci. USA v.89 Expression cloning of human cDNA encoding folypoly(γ-glutamate) synthetase and determination of its primary structure Garrow,T.A.;Admon,A.;Shane,B.
  30. Mol. Cell. Biol. v.9 Nonsence mutation in the dihydrofolate reductase gene affect RNA processing Urlaub,G.;Mitchell,P.J.;Ciudad,C.J.;Chasin,L.A.
  31. Bio Essays v.13 Multidrug resistant transgenic mice as a novel pharmacologic tool Mickish,G.H.;Pastan,I.;Gottesman,M.M.
  32. Cancer Res. v.50 Reversal of the multidrug resistance phenotype with cremophor EL, a common vehicle for water-insoluble vitamins and drugs Woodcock,D.M.;Jefferson,S.;Linsenmeyer,M.E.;Crowther,P.J.;Chojnowski,G.M.;Williams,B.;Bertoncello,I.
  33. Cancer Res. v.48 Genes amplified and overexpressed in human multidrug-resistant cell lines Bliek,A.M.V.;Baas,F.;Velde-Koerts,T.V.;Biedler,J.L.;Meyers,M.B.;Ozols,R.F.;Hamilton,T.C.;Joenje,H.;Borst,P.
  34. Cancer Res. v.50 Comparison of the cytotoxic effects of the high-and low-molecular-weight anticancer agents on multidrug-resistant Chinese hamster ovary cells in vitro Miyamoto,Y.;Oda,T.;Maeda,H.
  35. Mol. Cell. Biol. v.10 Two members of the mouse mdr gene family confer multidrug resistance with overlapping but distinct drug specificities Devault,A.;Gros,P.
  36. Mol. Cell. Biol. v.10 Physical mapping amplification and overexpression of the mouse mdr gene family in multidrug-resistant cells Raymond,M.;Rose,E.;Housman,D.E.;Gros,P.
  37. Cell v.71 Separation of drug transport and chloride channel functions of the human multidrug resistance P-glycoprotein Gill,D.R.;Hyde,S.C.;Higgins,C.F.;Valverde,M.A.;Mintenig,G.M.;Sepulveda,F.V.