The effect of leucovorin on the synthesis of methotrexate poly-gamma-glutamates in the MCF-7 human breast cancer cell line.
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.
D G
DG
Kennedy
H W
HW
Van den Berg
R
R
Clarke
R F
RF
Murphy
D001943:Breast Neoplasms / Q000378:metabolism*; D002460:Cell Line; D005260:Female; D006801:Humans; D002955:Leucovorin / Q000494:pharmacology*; D008727:Methotrexate / Q000031:analogs & derivatives* / Q000096:biosynthesis / Q000378:metabolism; D010452:Peptide Biosynthesis; D011099:Polyglutamic Acid / Q000031:analogs & derivatives / Q000096:biosynthesis*; D013762:Tetrahydrofolate Dehydrogenase / Q000032:analysis
D011099:Polyglutamic Acid; C014085:methotrexate polyglutamate; D013762:Tetrahydrofolate Dehydrogenase; D002955:Leucovorin; D008727:Methotrexate