Therapeutic targeting of a novel 6-substituted pyrrolo [2,3-d]pyrimidine thienoyl antifolate to human solid tumors based on selective uptake by the proton-coupled folate transporter

Molecular Pharmacology

Volumn 80, Issue 6, 2011, Pages 1096-1107

  Desmoulin, Sita Kugel ^a   Wang, Lei ^d   Hales, Eric ^a,c   Polin, Lisa ^a,c   White, Kathryn ^a   Kushner, Juiwanna ^a   Stout, Mark ^b   Hou, Zhanjun ^a,c   Cherian, Christina ^a,c   Gangjee, Aleem ^d   Matherly, Larry H ^a,c  

^a WAYNE STATE UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b CHILDREN'S HOSPITAL OF MICHIGAN   (United States)

^c KARMANOS CANCER INSTITUTE   (United States)

^d DUQUESNE UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ADENOSINE TRIPHOSPHATE; FOLIC ACID ANTAGONIST; PACLITAXEL; PEMETREXED; PHOSPHORIBOSYLGLYCINAMIDE FORMYLTRANSFERASE; PROTON COUPLED FOLATE TRANSPORTER;

ACUTE GRANULOCYTIC LEUKEMIA; AMINO ACID SUBSTITUTION; ANIMAL EXPERIMENT; ANIMAL MODEL; ANTINEOPLASTIC ACTIVITY; APOPTOSIS; ARTICLE; CANCER INHIBITION; CELL CYCLE PROGRESSION; CELL PROLIFERATION; CELL STRAIN HEPG2; COLONY FORMATION; COLORECTAL CARCINOMA; COMPETITIVE INHIBITION; CONTROLLED STUDY; DRUG CYTOTOXICITY; DRUG EFFICACY; DRUG METABOLISM; DRUG STRUCTURE; FEMALE; HELA CELL; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; HUMAN; HUMAN CELL; LIVER CELL CARCINOMA; MOUSE; NONHUMAN; OVARY CANCER; PH; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN TARGETING; PROTEIN TRANSPORT; REAL TIME POLYMERASE CHAIN REACTION; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; TUMOR CELL LINE; TUMOR MICROENVIRONMENT; TUMOR VOLUME;

ANIMALS; DOSE-RESPONSE RELATIONSHIP, DRUG; DRUG DELIVERY SYSTEMS; FEMALE; FOLIC ACID ANTAGONISTS; HELA CELLS; HEP G2 CELLS; HUMANS; MICE; MICE, INBRED ICR; MICE, SCID; NEOPLASMS; PROTON-COUPLED FOLATE TRANSPORTER; PYRIMIDINES; XENOGRAFT MODEL ANTITUMOR ASSAYS;

EID: 81555195479     PISSN: 0026895X     EISSN: 15210111     Source Type: Journal    
DOI: 10.1124/mol.111.073833     Document Type: Article

References (40)

1. Beardsley GP, Moroson BA, Taylor EC, and Moran RG (1989) A new folate antimetabolite, 5,10-dideaza-5,6,7,8-tetrahydrofolate is a potent inhibitor of de novo purine synthesis. J Biol Chem 264:328-333. (Pubitemid 19027608)
2. Chattopadhyay S, Moran RG, and Goldman ID (2007) Pemetrexed: biochemical and cellular pharmacology, mechanisms, and clinical applications. Mol Cancer Ther 6:404-417. (Pubitemid 46332443)
3. Deng Y, Wang Y, Cherian C, Hou Z, Buck SA, Matherly LH, and Gangjee A (2008) Synthesis and discovery of high affinity folate receptor-specific glycinamide ribonucleotide formyltransferase inhibitors with antitumor activity. J Med Chem 51:5052-5063.
4. Deng Y, Zhou X, Kugel Desmoulin S, Wu J, Cherian C, Hou Z, Matherly LH, and Gangjee A (2009) Synthesis and biological activity of a novel series of 6-substituted thieno[2,3-d]pyrimidine antifolate inhibitors of purine biosynthesis with selectivity for high affinity folate receptors over the reduced folate carrier and proton-coupled folate transporter for cellular entry. J Med Chem 52:2940-2951.
5. Elnakat H and Ratnam M (2004) Distribution, functionality and gene regulation of folate receptor isoforms: implications in targeted therapy. Adv Drug Deliv Rev 56:1067-1084. (Pubitemid 38496508)
6. Fais S, De Milito A, You H, and Qin W (2007) Targeting vacuolar H+-ATPases as a new strategy against cancer. Cancer Res 67:10627-10630. (Pubitemid 350145883)
7. Farber S and Diamond LK (1948) Temporary remissions in acute leukemia in children produced by folic acid antagonist, 4-aminopteroyl-glutamic acid. N Engl J Med 238:787-793.
8. Ganji V and Kafai MR (2009) Demographic, lifestyle, and health characteristics and serum B vitamin status are determinants of plasma total homocysteine concentration in the post-folic acid fortification period, 1999-2004. J Nutr 139:345-352.
9. Gibbs DD, Theti DS, Wood N, Green M, Raynaud F, Valenti M, Forster MD, Mitchell F, Bavetsias V, Henderson E, et al. (2005) BGC 945, a novel tumor-selective thymidylate synthase inhibitor targeted to alpha-folate receptor-overexpressing tumors. Cancer Res 65:11721-11728. (Pubitemid 41821733)
10. Goldman ID and Matherly LH (1985) The cellular pharmacology of methotrexate. Pharmacol Ther 28:77-102. (Pubitemid 15015465)
11. Helmlinger G, Yuan F, Dellian M, and Jain RK (1997) Interstitial pH and pO2 gradients in solid tumors in vivo: high-resolution measurements reveal a lack of correlation. Nat Med 3:177-182. (Pubitemid 27064702)
12. Hilgenbrink AR and Low PS (2005) Folate receptor-mediated drug targeting: from therapeutics to diagnostics. J Pharm Sci 94:2135-2146. (Pubitemid 41665275)
13. Hori H, Tran P, Carrera CJ, Hori Y, Rosenbach MD, Carson DA, and Nobori T (1996) Methylthioadenosine phosphorylase cDNA transfection alters sensitivity to depletion of purine and methionine in A549 lung cancer cells. Cancer Res 56:5653-5658. (Pubitemid 26422168)
14. Huang D, Zhang Y, and Chen X (2003) Analysis of intracellular nucleoside triphosphate levels in normal and tumor cell lines by high-performance liquid chromatography. J Chromatogr B Analyt Technol Biomed Life Sci 784:101-109. (Pubitemid 36009345)
15. Illei PB, Rusch VW, Zakowski MF, and Ladanyi M (2003) Homozygous deletion of CDKN2A and codeletion of the methylthioadenosine phosphorylase gene in the majority of pleural mesotheliomas. Clin Cancer Res 9:2108-2113. (Pubitemid 36687632)
16. Kugel Desmoulin S, Wang Y, Tait L, Hou Z, Cherian C, Gangjee A, and Matherly LH (2010a) Expression profiling of the major folate facilitative transporters in human tumors and normal tissues, in Proceedings of the Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington DC. pp 1103, Abstract 4546. American Association for Cancer Research, Philadelphia.
17. Kugel Desmoulin S, Wang Y, Wu J, Stout M, Hou Z, Fulterer A, Chang MH, Romero MF, Cherian C, Gangjee A, and Matherly LH (2010b) Targeting the proton-coupled folate transporter for selective delivery of 6-substituted pyrrolo[2,3-d]pyrimidine antifolate inhibitors of de novo purine biosynthesis in the chemotherapy of solid tumors. Mol Pharmacol 78:577-587.
18. Lowry OH, Rosebrough NJ, Farr AL, and Randall RJ (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193:265-275.
19. Martin GR and Jain RK (1994) Noninvasive measurement of interstitial pH profiles in normal and neoplastic tissue using fluorescence ratio imaging microscopy. Cancer Res 54:5670-5674. (Pubitemid 24346265)
20. Matherly LH, Hou Z, and Deng Y (2007) Human reduced folate carrier: translation of basic biology to cancer etiology and therapy. Cancer Metastasis Rev 26:111-128. (Pubitemid 46452186)
21. Matherly LH, Voss MK, Anderson LA, Fry DW, and Goldman ID (1985) Enhanced polyglutamylation of aminopterin relative to methotrexate in the Ehrlich ascites tumor cell in vitro. Cancer Res 45:1073-1078. (Pubitemid 15111262)
22. Mendelsohn LG, Worzalla JF, and Walling JM (1999) Preclinical and clinical evaluation of the glycinamide ribonucleotide formyltransferase inhibitors lometrexol and LY309887, in Anticancer Drug Development Guide: Antifolate Drugs in Cancer Therapy (Jackman AL ed) pp 261-280, Humana Press, Inc., Totowa, NJ.
23. Monahan BP and Allegra CJ (2006) Antifolates, in Cancer Chemotherapy and Biotherapy (Chabner BA, Longo DL ed) pp 91-124, Lippincott Williams & Wilkins, Philadelphia.
24. Nakai Y, Inoue K, Abe N, Hatakeyama M, Ohta KY, Otagiri M, Hayashi Y, and Yuasa H (2007) Functional characterization of human proton-coupled folate transporter/ heme carrier protein 1 heterologously expressed in mammalian cells as a folate transporter. J Pharmacol Exp Ther 322:469-476. (Pubitemid 47105788)
25. Qiu A, Jansen M, Sakaris A, Min SH, Chattopadhyay S, Tsai E, Sandoval C, Zhao R, Akabas MH, and Goldman ID (2006) Identification of an intestinal folate transporter and the molecular basis for hereditary folate malabsorption. Cell 127:917-928. (Pubitemid 44792250)
26. Qiu A, Min SH, Jansen M, Malhotra U, Tsai E, Cabelof DC, Matherly LH, Zhao R, Akabas MH, and Goldman ID (2007) Rodent intestinal folate transporters (SLC46A1): secondary structure, functional properties, and response to dietary folate restriction. Am J Physiol Cell Physiol 293:C1669-C1678. (Pubitemid 350085626)
27. Racanelli AC, Rothbart SB, Heyer CL, and Moran RG (2009) Therapeutics by cytotoxic metabolite accumulation: pemetrexed causes ZMP accumulation, AMPK activation, and mammalian target of rapamycin inhibition. Cancer Res 69:5467-5474.
28. Raghunand N, Altbach MI, van Sluis R, Baggett B, Taylor CW, Bhujwalla ZM, and Gillies RJ (1999) Plasmalemmal pH-gradients in drug-sensitive and drug-resistant MCF-7 human breast carcinoma xenografts measured by 31P magnetic resonance spectroscopy. Biochem Pharmacol 57:309-312. (Pubitemid 29056209)
29. Salazar MD and Ratnam M (2007) The folate receptor: what does it promise in tissue-targeted therapeutics? Cancer Metastasis Rev 26:141-152. (Pubitemid 46452188)
30. Shane B (1989) Folylpolyglutamate synthesis and role in the regulation of one-carbon metabolism. Vitam Horm 45:263-335.
31. Smith SG, Lehman NL, and Moran RG (1993) Cytotoxicity of antifolate inhibitors of thymidylate and purine synthesis to WiDr colonic carcinoma cells. Cancer Res 53:5697-5706. (Pubitemid 23360274)
32. Tsujimoto Y (1997) Apoptosis and necrosis: intracellular ATP level as a determinant for cell death modes. Cell Death Differ 4:429-434.
33. Varela-Moreiras G and Selhub J (1992) Long-term folate deficiency alters folate content and distribution differentially in rat tissues. J Nutr 122:986-991.
34. Wang L, Cherian C, Desmoulin SK, Polin L, Deng Y, Wu J, Hou Z, White K, Kushner J, Matherly LH, et al. (2010) Synthesis and antitumor activity of a novel series of 6-substituted pyrrolo[2,3-d]pyrimidine thienoyl antifolate inhibitors of purine biosynthesis with selectivity for high affinity folate receptors and the proton-coupled folate transporter over the reduced folate carrier for cellular entry. J Med Chem 53:1306-1318.
35. Wike-Hooley JL, Haveman J, and Reinhold HS (1984) The relevance of tumour pH to the treatment of malignant disease. Radiother Oncol 2:343-366. (Pubitemid 15166545)
36. Zhao R, Gao F, Hanscom M, and Goldman ID (2004) A prominent low-pH methotrexate transport activity in human solid tumors: contribution to the preservation of methotrexate pharmacologic activity in HeLa cells lacking the reduced folate carrier. Clin Cancer Res 10:718-727. (Pubitemid 38180440)
37. Zhao R and Goldman ID (2003) Resistance to antifolates. Oncogene 22(47):7431-7457. (Pubitemid 37487168)
38. Zhao R and Goldman ID (2007) The molecular identity and characterization of a proton-coupled folate transporter-PCFT; biological ramifications and impact on the activity of pemetrexed. Cancer Metastasis Rev 26:129-139. (Pubitemid 46452187)
39. Zhao R, Matherly LH, and Goldman ID (2009) Membrane transporters and folate homeostasis: intestinal absorption and transport into systemic compartments and tissues. Expert Rev Mol Med 11:e4.
40. Zhao R, Qiu A, Tsai E, Jansen M, Akabas MH, and Goldman ID (2008) The proton-coupled folate transporter: impact on pemetrexed transport and on antifolates activities compared with the reduced folate carrier. Mol Pharmacol 74:854-862.