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

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 re...

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Veröffentlicht in:Biochemical pharmacology 1986-09, Vol.35 (18), p.3053-3056
Hauptverfasser: Kennedy, D.G., Van den Berg, H.W., Clarke, R., Murphy, R.F.
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container_issue 18
container_start_page 3053
container_title Biochemical pharmacology
container_volume 35
creator Kennedy, D.G.
Van den Berg, H.W.
Clarke, R.
Murphy, R.F.
description 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.
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issn 0006-2952
1873-2968
language eng
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source MEDLINE; Elsevier ScienceDirect Journals
subjects Arachidonic Acid
Arachidonic Acids - pharmacology
Breast Neoplasms - drug therapy
Cell Count
Cell Line
Dipyridamole - therapeutic use
Drug Synergism
Female
Humans
Indomethacin - pharmacology
Methotrexate - therapeutic use
Polyglutamic Acid - metabolism
Time Factors
title Enhancement of methotrexate cytotoxicity towards the MDA.MB.436 human breast cancer cell line by dipyridamole: The role of methotrexate polyglutamates
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