Mechanisms of action of methotrexate

Immunopharmacology

Volumn 47, Issue 2-3, 2000, Pages 247-257

  Genestier, Laurent ^a   Paillot, Romain ^a   Quemeneur, Laurence ^a   Izeradjene, Kamel ^a   Revillard, Jean Pierre ^a  

^a UNIVERSITÉ LYON 1   (France)

Author keywords

[No Author keywords available]

Indexed keywords

FOLIC ACID; METHOTREXATE;

ANTIINFLAMMATORY ACTIVITY; APOPTOSIS; CELL DEATH; DRUG MECHANISM; HUMAN; IMMUNOSUPPRESSIVE TREATMENT; IN VITRO STUDY; PRIORITY JOURNAL; PURINE SYNTHESIS; REVIEW; T LYMPHOCYTE;

ANIMALS; ANTI-INFLAMMATORY AGENTS, NON-STEROIDAL; APOPTOSIS; ARTHRITIS, RHEUMATOID; HUMANS; IMMUNOSUPPRESSIVE AGENTS; METHOTREXATE; PURINE NUCLEOTIDES;

EID: 0034043034     PISSN: 01623109     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0162-3109(00)00189-2     Document Type: Article

References (78)

1. Allegra C.J., Chabner B.A., Drake J.C., Lutz R., Rodbard D., Jolivet J. Enhanced inhibition of thymidylate synthase by methotrexate polyglutamates. J. Biol. Chem. 260:1985;9720-9726.
2. Allegra C.J., Drake J.C., Jolivet J., Chabner B.A. Inhibition of phosphoribosyl-aminoimidazole-carboxamide transformylase by methotrexate and dihydrofolic acid polyglutamates. Proc. Natl. Acad. Sci. U. S. A. 82:1985;4881-4885.
3. Allegra C.J., Hoang K., Yeh G.C., Drake J.C., Baram J. Evidence for direct inhibition of de novo purine synthesis in human MCF-7 breast cells as a principal mode of metabolic inhibition by methotrexate. J. Biol. Chem. 262:1987;13520-13526.
4. Antony A.C., Kane M.A., Portillo R.M., Elwood P.C., Kolhouse J.F. Studies of the role of a particulate folate-binding protein in the uptake of 5-methyltetrahydrofolate by cultured human KB cells. J. Biol. Chem. 260:1985;14911-14917.
5. Asako H., Wolf R.E., Granger D.N. Leukocyte adherence in rat mesenteric venules: effects of adenosine and methotrexate. Gastroenterology. 104:1993;31-37.
6. Baggott J.E., Vaughn W.H., Hudson B.B. Inhibition of 5-aminoimidazole-4-carboxamide ribotide transformylase, adenosine deaminase and 5′-adenylate deaminase by polyglutamates of methotrexate and oxidized folates and by 5-aminoimidazole-4-carboxamide riboside and ribotide. Biochem. J. 236:1986;193-200.
7. Barry M.A., Behnke C.A., Eastman A. Activation of programmed cell death (apoptosis) by cisplatin, other anticancer drugs, toxins and hyperthermia. Biochem. Pharmacol. 40:1990;2353-2362.
8. Chabner P.A., Allegra C.J., Curt G.A., Clendeninn N.J., Baram J., Koisumi S., Drake J.C., Jolivet J. Polyglutamation of methotrexate. Is methotrexate a prodrug? J. Clin. Invest. 76:1985;907-912.
9. Chao N.J., Schmidt G.M., Niland J.C., Amylon M.D., Dagis A.C., Long G.D., Nademanee A.P., Negrin R.S., O'Donnell M.R., Parker P.M., Smith E.P., Snyder D.S., Stein A.S., Wong R.M., Blume K.G., Forman S.J. Cyclosporine, methotrexate, and prednisone compared with cyclosporine and prednisone for prophylaxis of acute graft-vs.-host disease. N. Engl. J. Med. 329:1993;1225-1230.
10. Chu E., Drake J.C., Boarman D., Baram J., Allegra C.J. Mechanism of thymidylate synthase inhibition by methotrexate in human neoplastic cell lines and normal human myeloid progenitor cells. J. Biol. Chem. 265:1990;8470-8478.
11. Cronstein B.N. Adenosine, an endogenous anti-inflammatory agent. J. Appl. Physiol. 76:1994;5-13.
12. Cronstein B.N., Eberle M.A., Gruber H.E., Levin R.I. Methotrexate inhibits neutrophil function by stimulating adenosine release from connective tissue cells. Proc. Natl. Acad. Sci. U. S. A. 88:1991;2441-2445.
13. Cronstein B.N., Hirschhom R. Adenosine and host defense. Williams M. Adenosine and Adenosine Receptors. 1990;475-500 Humana Press, Clifton, NJ.
14. Cronstein B.N., Levin R.I., Philips M., Hirschhorn R., Abramson S.B., Weissmann G. Neutrophil adherence to endothelium is enhanced via adenosine A1 receptors and inhibited via adenosine A2 receptors. J. Immunol. 148:1992;2201-2206.
15. Cronstein B.N., Naime D., Ostad E. The anti-inflammatory mechanism of methotrexate. Increased adenosine release at inflamed sites diminishes leukocyte accumulation in an in vivo model of inflammation. J. Clin. Invest. 92:1993;2675-2682.
16. Cronstein B.N., Rosenstein E.D., Kramer S.B., Weissmann G., Hirschhorn R. Adenosine; a physiologic modulator of superoxide anion generation by human neutrophils. Adenosine acts via an A2 receptor on human neutrophils. J. Immunol. 135:1985;1366-1371.
17. Da Silva C.P., De Oliveira C.R., De Lima M.C.P. Apoptosis as a mechanism of cell death induced by different chemotherapeutic drugs in human leukemic T lymphocytes. Biochem. Pharmacol. 51:1996;1331-1340.
18. Deeg J., Storb R., Weiden P.L., Raff R.F., Sale G.E., Atkinson K., Graham T.C., Thomas E.D. Cyclosporin A and methotrexate in canine marrow transplantation: engraftment, graft-versus-host disease, and induction of tolerance. Transplantation. 34:1982;30-35.
19. De Graaf D., Sharma R.C., Mechetner E.B., Schimke R.T., Roninson I.B. P-glycoprotein confers methotrexate resistance in 3T6 cells with deficient carrier-mediated methotrexate uptake. Proc. Natl. Acad. Sci. U. S. A. 93:1996;1238-1242.
20. Dicker A.P., Waltham M.C., Volkenandt M., Schweitzer B.I., Otter G.M., Schmid F.A., Sirotnak F.M., Bertino J.R. Methotrexate resistance in an in vivo mouse tumor due to a non-active-site dihydrofolate reductase mutation. Proc. Natl. Acad. Sci. U. S. A. 90:1993;11797-11801.
21. Elwood P.C., Kane M.A., Portillo R.M., Kolhouse J.F. The isolation, characterization, and comparison of the membrane-associated and soluble folate-binding proteins from human KB cells. J. Biol. Chem. 261:1986;15416-15423.
22. Endresen L. Pharmacology and general therapeutic principles of methotrexate. H.E.R.et al. Immunopharmacology in Autoimmune Diseases and Transplantation. 1992;127-138 Plenum, New York.
23. Fan J., Vitols K.S., Huennekens F.M. Biotin derivatives of methotrexate and folate. Synthesis and utilization for affinity purification of two membrane-associated folate transporters from L1210 cells. J. Biol. Chem. 266:1991;14862-14865.
24. Farber S., Toch R., Sears E., Pinkel D. Advances in chemotherapy of cancer in man. Greenstein H.A. Advances in Cancer Research. 1956;2-73 Academic Press, New York.
25. Firestein G.S., Paine M.M., Boyle D.L. Mechanisms of methotrexate action in rheumatoid arthritis. Arthritis Rheum. 37:1994;193-200.
26. Fournel S., Genestier L., Rouault J.-P., Lizard G., Flacher M., Assossou O., Revillard J.-P. Apoptosis without decrease of cell DNA content. FEBS Lett. 367:1995;188-192.
27. Friesen C., Herr I., Krammer P.H., Debatin K.-M. Involvement of the CD95 (APO-1/Fas) receptor/ligand system in drug-induced apoptosis in leukemia cells. Nat. Med. 2:1996;574-577.
28. Fry D.W., Yalowich J.C., Goldman I.D. Rapid formation of poly-gamma-glutamyl derivatives of methotrexate and their association with dihydrofolate reductase as assessed by high pressure liquid chromatography in the Ehrlich ascites tumor cell in vitro. J. Biol. Chem. 257:1982;1890-1896.
29. Galivan J. Evidence for the cytotoxic activity of polyglutamate derivatives of methotrexate. Mol. Pharmacol. 17:1980;105-110.
30. Genestier L., Paillot R., Bonnefoy-Berard N., Meffre G., Flacher M., Fèvre D., Liu Y.J., Le Bouteiller P., Waldmann H., Engelhard V.H., Banchereau J., Revillard J.-P. Fas independent apoptosis of activated T cells induced by antibodies to the HLA class I a1 domain. Blood. 90:1997;3629-3639.
31. Genestier L., Paillot R., Fournel S., Ferraro C., Miossec P., Revillard J.P. Immunosuppressive properties of methotrexate: apoptosis and clonal deletion of activated peripheral T cells. J. Clin. Invest. 102:1998;322-328.
32. + cells in murine acute graft-vs.-host reactions. J. Immunol. 142:1989;1867-1873.
33. Goldman I.D., Matherly L.H. The cellular pharmacology of methotrexate. Pharmacol. Ther. 28:1985;77-102.
34. Gruber H.E., Hoffer M.E., McAllister D.R., Laikind P.K., Lane T.A., Schmid-Schoenbein G.W., Engler R.L. Increased adenosine concentration in blood from ischemic myocardium by AICA riboside. Effects on flow, granulocytes, and injury. Circulation. 80:1989;1400-1411.
35. Heenen M., Laporte M., Noel J.C., de Graef C. Methotrexate induces apoptotic cell death in human keratinocytes. Arch. Dermatol. Res. 290:1998;240-245.
36. Henderson G.B. Folate-binding proteins. Annu. Rev. Nutr. 10:1990;319-335.
37. 3H]methotrexate. J. Biol. Chem. 259:1984;4558-4562.
38. Hirata S., Matsubara T., Saura R., Tateishi H., Hirohata K. Inhibition of in vitro vascular endothelial cell proliferation and in vivo neovascularization by low-dose methotrexate. Arthritis Rheum. 32:1989;1065-1073.
39. Jackson R.C., Harrap K.R. Studies with a mathematical model of folate metabolism. Arch. Biochem. Biophys. 158:1973;827-841.
40. Jansen G., Kathmann I., Rademaker B.C., Braakhuis B.J., Westerhof G.R., Rijksen G., Schornagel J.H. Expression of a folate binding protein in L1210 cells grown in low folate medium. Cancer Res. 49:1989;1959-1963.
41. Jansen G., Westerhof G.R., Jarmuszewski M.J.A., Kathmann I., Rijksen G., Schornage J.H. Methotrexate transport in variant human CCRF-CEM leukemia cells with elevated levels of the reduced folate carrier. J. Biol. Chem. 265:1990;18272-18277.
42. Jolivet J., Chabner B.A. Intracellular pharmacokinetics of methotrexate polyglutamates in human breast cancer cells. J. Clin. Invest. 72:1983;773-778.
43. Jolivet J., Schilsky R.L., Bailey B.D., Drake J.C., Chabner B.A. Synthesis, retention, and biological activity of methotrexate polyglutamates in cultured human breast cancer cells. J. Clin. Invest. 70:1982;351-360.
44. Kane M.A., Portillo R.M., Elwood P.C., Antony A.C., Kolhouse J.F. The influence of extracellular folate concentration on methotrexate uptake by human KB cells. Partial characterization of a membrane-associated methotrexate binding protein. J. Biol. Chem. 261:1986;44-49.
45. Kasibhatla S., Brunner T., Genestier L., Echeverri F., Mahboubi A., Green D.R. DNA damaging agents induce expression of Fas ligand and subsequent apoptosis in T lymphocytes via the activation of NF-kappa B and AP-1. Mol. Cell. 1:1998;543-551.
46. + T cells in mice tolerant to Staphylococcus aureus enterotoxin B. Nature. 349:1991;24.
47. Kizaki H., Shimada H., Ohsaka F., Sakurada T. Adenosine, deoxyadenosine, and deoxyguanosine induce DNA cleavage in mouse thymocytes. J. Immunol. 5:1988;1652-1657.
48. Mickisch G.H., Merlino G.T., Galski H., Gottesman M.M., Pastan I. Transgenic mice that express the human multidrug-resistance gene in bone marrow enable a rapid identification of agents that reverse drug resistance. Proc. Natl. Acad. Sci. U. S. A. 88:1991;547-551.
49. Morabito L., Montesinos M.C., Schreibman D.M., Balter L., Thompson L.F., Resta R., Carlin G., Huie M.A., Cronstein B.N. Methotrexate and sulfasalazine promote adenosine release by a mechanism that requires ecto-5′ nucleotidase mediated conversion of adenine nucleotides. J. Clin. Invest. 101:1998;295-300.
50. Moran R.G., Werkheiser W.C., Zakrzewski S.F. Folate metabolism in mammalian cells in culture: I. Partial characterization of the folate derivatives present in L1210 mouse leukemia cells. J. Biol. Chem. 251:1976;3569-3575.
51. Muller M., Strand S., Hug H., Heinemann E.M., Walczak H., Hofmann W.J., Stremmel W., Krammer P.H., Galle P.R. Drug-induced apoptosis in hepatoma cells is mediated by the CD95 (APO-1/Fas) receptor/ligand system and involves activation of wild-type p53. J. Clin. Invest. 99:1997;403-413.
52. Muller M., Wilder S., Bannasch D., Israeli D., Lehlbach K., Li-Weber M., Friedman S.L., Galle P.R., Stremmel W., Oren M., Krammer P.H. p53 activates the CD95 (APO-1/Fas) gene in response to DNA damage by anticancer drugs. J. Exp. Med. 188:1998;2033-2045.
53. Nash R.A., Pineiro L.A., Storb R., Deeg J.H., Fitzsimmons W.E., Furlong T., Hansen J.A., Gooley T., Maher R.M., Martin P., McSweeney P.A., Sullivan K.M., Anasetti C., Fay J.W. FK506 combination with methotrexate for the prevention of graft-vs.-host disease after marrow transplantation from matched unrelated donors. Blood. 88:1996;3634-3641.
54. Nash R.A., Pepe M.S., Storb R., Longton G., Pettinger M., Anasetti C., Appelbaum F.R., Bowden R.A., Deeg H.J., Doney K., Martin P.J., Sullivan K.M., Sanders J., Witherspoon R.P. Acute graft-vs.-host disease: analysis of risk factors after allogeneic marrow transplantation and prophylaxis with cyclosporine and methotrexate. Blood. 80:1992;1838-1845.
55. Olsen S.L., O'Connell J.B., Bristow M.R., Renlund D.G. Methotrexate as an adjunct in the treatment of persistent mild cardiac allograft rejection. Transplantation. 50:1990;773-775.
56. Owens A.H., Santos G.W. The effect of cytotoxic drugs on graft-vs.-host disease in mice. Transplantation. 11:1971;378-382.
57. Paillot R., Genestier L., Fournel S., Ferraro C., Miossec P., Revillard J.P. Activation-dependent lymphocyte apoptosis induced by methotrexate. Transplant. Proc. 30:1998;2348-2350.
58. Pearce H.L., Safa A.R., Bach N.J., Winter M.A., Cirtain M.C., Beck W.T. Essential features of the P-glycoprotein pharmacophore as defined by a series of reserpine analogs that modulate multidrug resistance. Proc. Natl. Acad. Sci. U. S. A. 77:1989;2919-2922.
59. Price E.M., Ratnam M., Rodeman K.M., Freisheim J.H. Characterization of the methotrexate transport pathway in murine L1210 leukemia cells: involvement of a membrane receptor and a cytosolic protein. Biochemistry. 27:1988;7853-7858.
60. Refaeli Y., Van Parijs L., London C.A., Tschopp J., Abbas A.K. Biochemical mechanisms of IL-2-regulated Fas-mediated T cell apoptosis. Immunity. 8:1998;615-623.
61. Roberts P.A., Newby A.C., Hallett M.B., Campbell A.K. Inhibition by adenosine of reactive oxygen metabolite production by human polymorphonuclear leukocytes. Biochem. J. 227:1985;669-674.
62. Rosowsky A., Wright J.E., Holden S.A., Waxman D.J. Influence of lipophilicity and carboxyl group content on the rate of hydroxylation of methotrexate derivatives by aldehyde oxidase. Biochem. Pharmacol. 40:1990;851-857.
63. Salmon J.E., Cronstein B.N. Fc gamma receptor-mediated functions in neutrophils are modulated by adenosine receptor occupancy. A1 receptors are stimulatory and A2 receptors are inhibitory. J. Immunol. 145:1990;2235-2240.
64. Segal R., Yaron M., Tartakovsky B. Methotrexate: mechanism of action in rheumatoid arthritis. Semin. Arthritis Rheum. 20:1990;190-200.
65. Sirotnak F.M., Goutas L.J., Mines L.S. Extent of the requirement for folate transport by L1210 cells for growth and leukemogenesis in vivo. Cancer Res. 45:1985;4732-4734.
66. Sobrero A., Aschele C., Rosso R., Nicolin A., Bertino J.R. Rapid development of resistance to antifolates in vitro: possible clinical implication. J. Natl. Cancer Inst. 83:1991;24-28.
67. Spencer H.T., Sorrentino B.P., Pui C.-H., Chunduru S.K., Sleep S.E.H., Nlakley R.L. Mutation in the gene for human dihydrofolate reductase: an unlikely cause of clinical relapse in pediatric leukemia after therapy with methotrexate. Leukemia. 10:1996;439-446.
68. Storb R., Deeg H.J., Farewell V., Doney K., Appelbaum F., Beatty P., Bensinger W., Buckner C.D., Clift R., Hansen J., Hill R., Longton G., Lum L., Martin P., McGuffin R., Sanders J., Slinger J., Stewart P., Sullivan K., Witherspoon R., Thomas E.D. Marrow transplantation for severe aplastic anemia: methotrexate alone compared with a combination of methotrexate and cyclosporine for prevention of acute graft-versus-host disease. Blood. 68:1986;119-125.
69. Storb R., Deeg H.J., Whitehead J., Appelbaum F., Beatty P., Bensinger W., Buckner D., Clift R., Doney K., Farewell V., Hansen J., Hill R., Lum L., Martin P., McGuffin R., Sanders J., Stewart P., Sullivan K., Witherspoon R., Yee G., Thomas E.D. Methotrexate and cyclosporine compared with cyclosporine alone for prophylaxis of acute graft-vs.-host disease after marrow transplantation for leukemia. N. Engl. J. Med. 314:1986;729-735.
70. Storb R., Epstein R.B., Graham T.C., Thomas E.D. Methotrexate regimens for control of graft-versus-host in dogs with allogeneic marrow graft. Transplantation. 9:1970;240-246.
71. Sullivan K.M., Storb R., Buckner D., Ferer A., Fisher L., Weiden P.L., Witherspoon R.P., Appelbaum F.R., Banaji M., Hansen J., Martin P., Sanders J.E., Singer J., Thomas D. Graft-versus-host disease as adoptive immunotherapy in patients with advanced hematologic neoplasms. N. Engl. J. Med. 320:1989;828-834.
72. Szeto D.W., Cheng Y.C., Rosowsky A., Yu C.S., Modest E.J., Piper J.R., Temple C. Jr., Elliott R.D., Rose J.D., Montgomery J.A. Human thymidylate synthetase: III. Effects of methotrexate and folate analogs. Biochem. Pharmacol. 28:1979;2633-2637.
73. Valerino D.M., Johns D.G., Zaharko D.S., Oliverio V.T. Studies of the metabolism of methotrexate by intestinal flora: I. Identification and study of biological properties of the metabolite 4-amino-4-deoxy-N-10-methylpteroic acid. Biochem. Pharmacol. 21:1972;821-831.
74. Weinblatt M.E., Coblyn J.S., Fox D.A., Fraser P.A., Holdsworth D.E., Glass D.N., Trentham D.E. Efficacy of low-dose methotrexate in rheumatoid arthritis. N. Engl. J. Med. 312:1985;818-822.
75. White J.C. Recent concepts on the mechanism of action of methotrexate. Cancer Treat. Rep. 65:1981;3-12.
76. White J.C., Goldman I.D. Mechanism of action of methotrexate: IV. Free intracellular methotrexate required to suppress dihydrofolate reduction to tetrahydrofolate by Ehrlich ascites tumor cells in vitro. Mol. Pharmacol. 12:1976;711-719.
77. White J., Herman A., Pullen A.M., Kubo R., Kappler J.W., Marrack P. The V beta-specific superantigen staphylococcal enterotoxin B: stimulation of mature T cells and clonal deletion in neonatal mice. Cell. 56:1989;27-35.
78. Williams H.J., Wilkens R.F., Samuelson C.O., Alarcon G.S., Guttadauria M., Yarboro C., Polisson R.P., Weiner S.R., Luggen M.E., Billingsley L.M., Dahl S.L., Egger M.L., Reading J.C., Ward J.R. Comparison of low-dose oral pulse methotrexate and placebo in the treatment of rheumatoid arthritis: a controlled clinical trial. Arthritis Rheum. 28:1985;721-730.