Enhancement of methotrexate cytotoxicity towards the MDA.MB.436 human breast cancer cell line by dipyridamole. The role of methotrexate polyglutamates

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

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

Abstract

MTX and dipyridamole are synergistic in their toxicity towards the MDA.MB.436 human breast cancer cell line. Dipyridamole increases net MTX uptake into the cells and increases the intracellular levels of MTXG7 to G10, the highest molecular weight polyglutamyl derivatives of MTX detected. During a recovery period, after completion of exposure to MTX with and without dipyridamole, levels of MTXG7 to G10 remained elevated in dipyridamole treated cells by comparison with controls. Dipyridamole, which has no intrinsic effect on cell growth, transforms a cytostatic response of MDA.MB.436 cells towards MTX into a cytotoxic response. The effect of dipyridamole is not mediated through an increase in prostacyclin biosynthesis.

Original languageEnglish (US)
Pages (from-to)3053-3056
Number of pages4
JournalBiochemical Pharmacology
Volume35
Issue number18
DOIs
StatePublished - Sep 15 1986
Externally publishedYes

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