Abstract
Intracellular levels of folate or methotrexate (MTX) polyglutamates are regulated at least in part by the enzyme, folylpolyglutamate synthase (FPGS), which is responsible for synthesis, and γ-glutamate hydrolase (GGH), which catalyzes the hydrolysis of polyglutamates to monbglutamate forms.1 Decreased accumulation of long chain polyglutamates of methotrexate (MTX) may result from decreased FPGS activity or increased GGH activity. Previous studies showed that natural resistance to MTX in soft tissue sarcomas is associated with the inability of these cells to accumulate long chain MTX polyglutamates after exposure to this drug.2,3 As no appreciable difference of FPGS activity was observed between MTX-resistant and sensitive cells, we measured GGH activity in these cell lines and found increased levels of this enzyme in MTX resistant soft tissue sarcoma cell lines.
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© 1993 Springer Science+Business Media New York
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Li, W.W., Waltham, M., Tong, W., Schweitzer, B.I., Bertino, J.R. (1993). Increased Activity of γ-Glutamyl Hydrolase in Human Sarcoma Cell Lines: A Novel Mechanism of Intrinsic Resistance to Methotrexate (MTX). In: Ayling, J.E., Nair, M.G., Baugh, C.M. (eds) Chemistry and Biology of Pteridines and Folates. Advances in Experimental Medicine and Biology, vol 338. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-2960-6_131
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DOI: https://doi.org/10.1007/978-1-4615-2960-6_131
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