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Growth-inhibitory effects of 5,10-dideazatetrahydrofolic acid on variant murine L1210 and human CCRF-CEM leukemia cells with different membrane-transport characteristics for (anti)folate compounds

Cancer Chemotherapy and Pharmacology volume 28, pages 115–117 (1991)Cite this article

Summary

5,10-Dideazatetrahydrofolic acid (DDATHF) is a potent inhibitor of glycinamide ribonucleotide transformylase, one of the folate-dependent key enzymes in de novo purine biosynthesis. The present report demonstrates that multiple membrane-transport routes may be involved in the cellular uptake of DDATHF. These routes include the classic reduced folate carrier and a membrane-associated folate-binding protein (mFBP). The role of an mFBP in the uptake of DDATHF was suggested from observations that (a) the mFBP showed a very high binding affinity for DDATHF, (b) murine and human leukemia cells expressing an mFBP were highly sensitive to growth inhibition by DDATHF, and (c) protection against this growth inhibition could be achieved using folic acid rather than reduced folate compounds.

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Affiliations

  1. Laboratory of Medical Enzymology, Department of Haematology, University Hospital Utrecht, The Netherlands

    Gert Rijksen

  2. Department of Internal Medicine, Netherlands Cancer Institute, Amsterdam, The Netherlands

    Jan H. Schornagel

  3. Oncology Department, Free University Hospital, P. O. Box 7057, 1007 MB, Amsterdam, The Netherlands

    Gerrit Jansen, G. Robbin Westerhof & Ietje Kathmann

Authors
  1. Gerrit Jansen
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  2. G. Robbin Westerhof
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  3. Ietje Kathmann
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  4. Gert Rijksen
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  5. Jan H. Schornagel
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Additional information

This study was supported by the Dutch Cancer Society (grant IKA-89-34)

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Jansen, G., Westerhof, G.R., Kathmann, I. et al. Growth-inhibitory effects of 5,10-dideazatetrahydrofolic acid on variant murine L1210 and human CCRF-CEM leukemia cells with different membrane-transport characteristics for (anti)folate compounds. Cancer Chemother. Pharmacol. 28, 115–117 (1991). https://doi.org/10.1007/BF00689699

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  • DOI: https://doi.org/10.1007/BF00689699

Keywords

  • Folate
  • Leukemia Cell
  • Purine
  • Cellular Uptake
  • High Binding Affinity