Efficient utilization of the reduced folate carrier in CCRF-CEM human leukemic lymphoblasts by the potent antifolate N(α)-(4-amino-4-deoxypteroyl)-N(δ)-hemiphthaloyl-L-ornithine (PT523) and its B-ring analogues

Biochemical Pharmacology

Volumn 60, Issue 1, 2000, Pages 41-46

  Wright, Joel E ^a   Vaidya, Chitra M ^a   Chen, Ying Nan ^a   Rosowsky, Andre ^a  

^a HARVARD MEDICAL SCHOOL   (United States)

Author keywords

dihydrofolate reductase; N( ) (4 amino 4 deoxypteroyl) N( ) hemiphthaloyl L ornithine (PT523) analogues; reduced folate carrier

Indexed keywords

AMINOPTERIN; AMINOPTERIN DERIVATIVE; DIHYDROFOLATE REDUCTASE INHIBITOR; METHOTREXATE; NALPHA (4 AMINO 4 DEOXYPTEROYL) NDELTA HEMIPHTHALOYLORNITHINE; REDUCED FOLATE CARRIER;

ARTICLE; CELL CULTURE; CONTROLLED STUDY; CYTOTOXICITY; DRUG UPTAKE; HUMAN; HUMAN CELL; IN VITRO STUDY; LEUKEMIA CELL LINE; PRIORITY JOURNAL;

ANTIMETABOLITES, ANTINEOPLASTIC; ANTINEOPLASTIC AGENTS; BIOLOGICAL TRANSPORT; CARRIER PROTEINS; DRUG INTERACTIONS; DRUG SCREENING ASSAYS, ANTITUMOR; FOLIC ACID ANTAGONISTS; HUMANS; LEUKEMIA; MEMBRANE PROTEINS; MEMBRANE TRANSPORT PROTEINS; METHOTREXATE; ORNITHINE; PTERINS; TUMOR CELLS, CULTURED;

EID: 0034097601     PISSN: 00062952     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0006-2952(00)00294-X     Document Type: Article

References (27)

1. α-(4-amino-4-deoxypteroyl)-L-ornithine derivatives Synthesis and in vitro antitumor activity . J Med Chem. 31:1988;1332-1337.
2. δ-hemiphthaloyl-L-ornithine. Pteridines. 1:1989;91-98.
3. Rhee M.S., Galivan J., Wright J.E., Rosowsky A. Biochemical studies on PT523, a potent nonpolyglutamatable antifolate, in cultured cells. Mol Pharmacol. 45:1994;783-791.
4. ω-hemiphthaloyl-α,ω-diaminoalkanoic acid analogues of aminopterin and 3′,5′-dichloroaminopterin. J Med Chem. 37:1994;2167-2174.
5. Chen G., Wright J.E., Rosowsky A. Dihydrofolate reductase binding and cellular uptake of nonpolyglutamatable antifolates Correlates of cytotoxicity toward methotrexate sensitive and -resistant human head and neck squamous carcinoma cells . Mol Pharmacol. 48:1995;758-765.
6. Westerhof G.R., Schornagel J.H., Kathmann I., Jackman A.L., Rosowsky A., Forsch R.A., Hynes J.B., Boyle F.T., Peters G.J., Pinedo H.M., Jansen G. Carrier- and receptor-mediated transport of folate antagonists targeting folate dependent enzymes Correlates of molecular structure and biological activity . Mol Pharmacol. 48:1995;459-471.
7. δ-hemiphthaloyl-L-ornithine (PT523). J Med Chem. 41:1998;5310-5319.
8. Koizumi S., Curt G.A., Fine R.L., Griffin J.D., Chabner B.A. Formation of methotrexate polyglutamates in purified myeloid precursor cells from normal human bone marrow. J Clin Invest. 75:1985;1008-1014.
9. Fry D.W., Anderson L.A., Borst M., Goldman I.D. Analysis of the role of membrane transport and polyglutamylation of methotrexate in the gut and Ehrlich tumor in vivo as factors in drug sensitivity and selectivity. Cancer Res. 43:1983;1087-1092.
10. van der Veer L.J., Westerhof G.R., Rijksen G., Schornagel J.H., Jansen G. Cytotoxicity of methotrexate and trimetrexate and its reversal by folinic acid in human leukemic CCRF-CEM cells with carrier-mediated and receptor-mediated folate uptake. Leuk Res. 13:1989;981-987.
11. Wright J.E., Rosowsky A., Cucchi C.A., Flatow J., Frei E. III. Methotrexate and γ-tert-butyl methotrexate transport in CEM and CEM/MTX human leukemic lymphoblasts. Biochem Pharmacol. 46:1993;871-876.
12. Pizzorno G., Cashmore A.R., Moroson B.A., Cross A.D., Smith A.K., Marling-Cason M., Kamen B.A., Beardsley G.P. 5,10-Dideazatetrahydrofolic acid (DDATHF) transport in CCRF-CEM and MA104 cell lines. J Biol Chem. 268:1993;1017-1023.
13. Rosowsky A. PT523 and other aminopterin analogues with a hemiphthaloyl-L-ornithine side chain Exceptionally tight-binding inhibitors of dihydrofolate reductase which are transported by the reduced folate carrier but cannot form polyglutamates . Curr Med Chem. 6:1999;329-353.
14. Taylor E.C., Palmer D.C., George T.J., Fletcher S.R., Tseng C.P., Harrington P.J., Beardsley G.P. Synthesis and biological activity of L-5-deazafolic acid and L-5-deazaaminopterin Synthetic strategies to 5-deazapteridines . J Med Chem. 48:1983;4852-4860.
15. Srinivasan A., Broom A.D. Pyridopyrimidines. 12. Synthesis of 8-deaza analogues of aminopterin and folic acid. J Org Chem. 46:1981;1777-1781.
16. Foley G.E., Lazarus H., Farber S., Uzman B.G., Boone B.A., McCarthy R.E. Continuous culture of human lymphoblasts from peripheral blood of a child with acute leukemia. Cancer. 18:1965;522-529.
17. Sirotnak F.M. Correlates of folate analog transport, pharmacokinetics and selective antitumor action. Pharmacol Ther. 8:1980;71-103.
18. Kuehl M., Brixner D.I., Broom A.D., Avery T.L., Blakley R.L. Cytotoxicity, uptake, polyglutamate formation, and antileukemic effects of 8-deaza analogues of methotrexate and aminopterin in mice. Cancer Res. 48:1988;1481-1488.
19. Johnson J.M., Meiering E.M., Wright J.E., Pardo J., Rosowsky A., Wagner G. NMR solution structure of the antitumor compound PT523 and NADPH in the ternary complex with human dihydrofolate reductase. Biochemistry. 36:1997;4399-4411.
20. Henderson G.B., Strauss B.P. Characteristics of a novel transport system for folate compounds in wild-type and methotrexate-resistant L1210 cells. Cancer Res. 50:1990;1709-1714.
21. Sierra E.E., Brigle K.E., Spinella M.J., Goldman I.D. pH dependence of methotrexate transport by the reduced folate carrier and the folate receptor in L1210 cells. Further evidence for a third route mediated at low pH. Biochem Pharmacol. 53:1997;223-231.
22. Kumar C.K., Moyer M.P., Dudeja P.K., Said H.M. A protein-tyrosine kinase-regulated, pH-dependent, carrier-mediated uptake system for folate in human normal colonic epithelial cell line NCM460. J Biol Chem. 272:1997;6226-6231.
23. 10-methylfolic acid. J Med Chem. 29:1986;1080-1087.
24. Sirotnak F.M., Chello P.L., DeGraw J.I., Piper J.R., Montgomery J.A. Membrane transport and the molecular basis for selective antitumor action of folate analogs. Sartorelli A.C., Lazo J.S., Bertino J.R. Molecular Actions and Targets for Cancer Chemotherapeutic Agents. 1981;349-384 Academic Press, New York.
25. Jansen G, Receptor- and carrier-mediated transport systems for folates and antifolates. In: Antifolate Drugs in Cancer Therapy (Ed. Jackman AL), pp. 293-321. Humana Press, Totowa, NJ, 1999.
26. Schlemmer R., Sirotnak F.M. Structural preferences among folate compounds and their analogues for ATP-mediated efflux by inside-out plasma membrane vesicles derived from L1210 cells. Biochem Pharmacol. 49:1995;1427-1433.
27. Bebawy M., Morris M.B., Roufogalis B.D. A continuous fluorescence assay for the study of P-glycoprotein-mediated drug efflux using inside-out membrane vesicles. Anal Biochem. 268:1999;270-277.