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. 1979 May;15(5):730–734. doi: 10.1128/aac.15.5.730

Antifolate Activity of Isoaminopterin in HeLa Cells

Hortencia Rosemond-Hornbeak 1, M G Nair 2
PMCID: PMC352745  PMID: 525990

Abstract

The antifolate activity and the transport characteristics of isoaminopterin (IA) in HeLa cells were studied and compared with those of methotrexate (MTX). Both IA and MTX inhibited the incorporation of [2-14C]deoxyuridine into HeLa cell DNA by 50% at a concentration of 0.09 μM by 8 h postaddition of the compounds. Unlike MTX, the inhibition of DNA synthesis by IA was time dependent and reached a maximum at 24 h. IA-induced inhibition was due to interference with folate metabolism, since it could be completely reversed with N5-formyl-tetrahydrofolate. Competitive transport experiments between IA and either radiolabeled MTX or radiolabeled folate showed that IA preferentially uses the reduced folate/MTX transport system. IA inhibited MTX uptake by 50% at a concentration of 6.8 μM but had a negligible effect on folate transport.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. BURKITT D., HUTT M. S., WRIGHT D. H. THE AFRICAN LYMPHOMA: PRELIMINARY OBSERVATIONS ON RESPONSE TO THERAPY. Cancer. 1965 Apr;18:399–410. doi: 10.1002/1097-0142(196504)18:4<399::aid-cncr2820180402>3.0.co;2-g. [DOI] [PubMed] [Google Scholar]
  2. Bertino J. R., Johns D. G. Folate antagonists. Annu Rev Med. 1967;18:27–34. doi: 10.1146/annurev.me.18.020167.000331. [DOI] [PubMed] [Google Scholar]
  3. HITCHINGS G. H., ELION G. B. Chemical suppression of the immune response. Pharmacol Rev. 1963 Jun;15:365–405. [PubMed] [Google Scholar]
  4. Horne D. W., Briggs W. T., Wagner C. A functional, active transport system for methotrexate in freshly isolated hepatocytes. Biochem Biophys Res Commun. 1976 Jan 12;68(1):70–76. doi: 10.1016/0006-291x(76)90011-5. [DOI] [PubMed] [Google Scholar]
  5. Hutchison D. J. Antifolate resistance and the genetic control of dihydrofolate reductase activity. Ann N Y Acad Sci. 1971 Nov 30;186:172–181. doi: 10.1111/j.1749-6632.1971.tb31140.x. [DOI] [PubMed] [Google Scholar]
  6. Nair M. G., Baugh C. M. Synthesis and biological evaluation of isofolic acid. J Med Chem. 1974 Feb;17(2):223–226. doi: 10.1021/jm00248a017. [DOI] [PubMed] [Google Scholar]
  7. Nair M. G., Campbell P. T., Baugh C. M. Synthesis of 10-thiofolic acid. A potential antibacterial and antitumor agent. J Org Chem. 1975 Jun 13;40(12):1745–1748. doi: 10.1021/jo00900a015. [DOI] [PubMed] [Google Scholar]
  8. Nair M. G., Campbell P. T. Folate analogues altered in the C9-N10 bridge region. 10-Oxafolic acid and 10-oxaaminopterin. J Med Chem. 1976 Jun;19(6):825–829. doi: 10.1021/jm00228a018. [DOI] [PubMed] [Google Scholar]
  9. Nair M. G., Mercer L. P., Baugh C. M. Synthesis and antifolate activity of isoaminopterin. J Med Chem. 1974 Dec;17(12):1268–1272. doi: 10.1021/jm00258a007. [DOI] [PubMed] [Google Scholar]
  10. ROSS G. T., GOLDSTEIN D. P., HERTZ R., LIPSETT M. B., ODELL W. D. SEQUENTIAL USE OF METHOTREXATE AND ACTINOMYCIN D IN THE TREATMENT OF METASTATIC CHORIOCARCINOMA AND RELATED TROPHOBLASTIC DISEASES IN WOMEN. Am J Obstet Gynecol. 1965 Sep 15;93:223–229. doi: 10.1016/0002-9378(65)90661-7. [DOI] [PubMed] [Google Scholar]
  11. Rosemond-Hornbeak H., Nair M. G. Transport and inhibitory activity of new folate analogues in HeLa cells. Mol Pharmacol. 1978 Mar;14(2):299–305. [PubMed] [Google Scholar]
  12. Thomas E. D., Storb R. The effect of amethopterin on the immune response. Ann N Y Acad Sci. 1971 Nov 30;186:467–474. doi: 10.1111/j.1749-6632.1971.tb47002.x. [DOI] [PubMed] [Google Scholar]
  13. Weinstein G. D. Biochemical and pathophysiological rationale for amethopterin in psoriasis. Ann N Y Acad Sci. 1971 Nov 30;186:452–466. doi: 10.1111/j.1749-6632.1971.tb47001.x. [DOI] [PubMed] [Google Scholar]

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