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Effects of verapamil on uptake and in vitro toxicity of anthracyclines in human leukemic blastcells
Author(s) -
Tidefelt U.,
SundmanEngberg B.,
Paul C.
Publication year - 1988
Publication title -
european journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.904
H-Index - 84
eISSN - 1600-0609
pISSN - 0902-4441
DOI - 10.1111/j.1600-0609.1988.tb00846.x
Subject(s) - verapamil , daunorubicin , doxorubicin , intracellular , cytotoxicity , pharmacology , in vitro , anthracycline , toxicity , leukemia , chemistry , chemotherapy , medicine , calcium , biochemistry , cancer , breast cancer
The effect of a calcium channel blocker, verapamil, on intracellular uptake and cytotoxicity of anthracyclines in vitro was studied on leukemic cells from 32 patients with acute non‐lymphoblastic leukemia. Cells were isolated from peripheral blood or bone‐marrow and incubated with a concentration of 0.2 μmol/l, 0.5 μmol/l and/or 1.0 μmol/l of doxorubicin or daunorubicin in the absence and presence of verapamil at a concentration of 2 μmol/l and/or 10 μmol/l. Intracellular uptake was determined at the end of the incubations by photofluorometer and the in vitro cytotoxicity was determined after 5 days culturing in liquid medium by dye exclusion according to Weisenthal. Verapamil significantly increased the intracellular uptake of anthracyclines 0.5 μmol/l and 1.0 μmol/l and the cytotoxic effect of anthracyclines 0.2 μmol/l and 0.5 μmol/l and affected doxorubicin and daunorubicin equally. There were no significant differences between the two concentrations of verapamil. Cells from different FAB‐groups were equally affected by verapamil. The effect on intracellular uptake was higher in cells from patients who were resistant to therapy compared to those who achieved a complete remission. We conclude that verapamil has an effect on intracellular uptake and cytotoxicity of anthracyclines on tumor cells from patients with acute non‐lymphoblastic leukemia. The prognostic and therapeutic relevance of this has to be further evaluated.