New Approach to Antifolate Treatment of Certain Cancers as Demonstrated in Tissue Culture

The selective toxicity of antifolates for a variety of cancers can be improved, as illustrated by the combined administration of N5-methyltetrahydrofolate and methotrexate in tissue culture. When a variety of neoplastic cell types characterized by a deficiency of vitamin B12-dependent N5-methyltetra...

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Bibliographic Details
Published inProceedings of the National Academy of Sciences - PNAS Vol. 72; no. 10; pp. 4018 - 4022
Main Authors Halpern, Richard M., Halpern, Barbara C., Clark, Brian R., Ashe, Hilary, Hardy, Dorothy N., Jenkinson, Pamela Y., Chou, Shao-Chia, Smith, Roberts A.
Format Journal Article
LanguageEnglish
Published United States National Academy of Sciences of the United States of America 01.10.1975
National Acad Sciences
Subjects
Adults
Animals
Carcinoma, Ehrlich Tumor - drug therapy
Cell Division - drug effects
Cell growth
Cells, Cultured
Cultured cells
Epithelial cells
Female
Fibroblasts - drug effects
Folic acid antagonists
Formyltetrahydrofolates
Humans
Leucovorin - therapeutic use
Leukemia
Leukemia L1210 - drug therapy
Leukemia, Myeloid - drug therapy
Liver
Liver - drug effects
Methotrexate - pharmacology
Methotrexate - therapeutic use
Mice
Neoplasms, Experimental - drug therapy
Rats
Tetrahydrofolates
Tetrahydrofolates - pharmacology
Tetrahydrofolates - therapeutic use
Tissue culture techniques
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Summary:The selective toxicity of antifolates for a variety of cancers can be improved, as illustrated by the combined administration of N5-methyltetrahydrofolate and methotrexate in tissue culture. When a variety of neoplastic cell types characterized by a deficiency of vitamin B12-dependent N5-methyltetrahydrofolate methyltransferase (5-methyltetrahydropteroyl-L-glutamate:L-homocysteine S-methyltransferase, EC 2.1.1.13) and normal adult cells are grown in media containing methotrexate and either N5-methyltetrahydrofolate or N5-formyltetrahydrofolate, not only is the selective toxicity of methotrexate demonstrated, but the advantage of using N5-methyltetrahydrofolate in place of N5-formyltetrahydrofolate is also revealed. The implications and applications of this particular combination in the treatment of human cancer are discussed.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.72.10.4018