The effect of leucovorin on the synthesis of methotrexate poly-γ-glutamates in the MCF-7 human breast cancer cell line

D. G. Kennedy, H. W. Van Den Berg, R. Clarke, R. F. Murphy

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

Abstract

The modulating effects of leucovorin on the synthesis of methotrexate (MTX) polyglutamates in the MCF-7 human breast cancer cell line have been investigated using a paired-ion high performance liquid chromatography (HPLC) system. Leucovorin decreased the intracellular level of MTX and profoundly affected polyglutamate synthesis irrespective of whether it was administered with or after MTX. Inhibition of MTX polyglutamate synthesis was also observed when concentrations of leucovorin too low to affect intracellular levels of MTX were employed. Leucovorin did not promote efflux of MTX from the MCF-7 cells and did not affect the distribution of the retained drug amongst the various polyglutamate forms.

Original languageEnglish (US)
Pages (from-to)2897-2903
Number of pages7
JournalBiochemical Pharmacology
Volume34
Issue number16
DOIs
StatePublished - Aug 15 1985
Externally publishedYes

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