Heparin reverses Rhodamine 123 extrusion by multidrug resistant cells.
The effect of heparin as a reversing agent of multidrug resistance (MDR) was tested on normal mononuclear cells from 24 healthy volunteers and leukaemic cells from 12 acute myeloid leukaemia, five chronic myeloid leukaemia, five acute lymphoid leukaemia and three chronic lymphoid leukaemia patients. Two cell lines were used as controls, the human erythroleukaemia K562 and its vincristine-resistant derivative K562-Lucena 1. Heparin was not cytotoxic by itself as determined using a MTT assay and cell counts. MDR modulation was assessed by Rhodamine 123 extrusion using flow-cytometry. Modulation of the resistant cell line was produced by the classical reversing agent verapamil and also by heparin, the same being observed in normal and leukaemic cells and being independent of the type of leukaemia. Our work suggests that heparin may be considered a potential MDR modulator.
Maia
R C
RC
Serviço de Pesquisa Básica, Instituto Nacional de Câncer, Rio de Janeiro, Brazil.
Wagner
K
K
Cabral
R H
RH
Rumjanek
V M
VM
D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D018432:Drug Resistance, Multiple; D005434:Flow Cytometry; D005456:Fluorescent Dyes; D006493:Heparin / Q000494:pharmacology*; D006801:Humans; D007938:Leukemia / Q000097:blood*; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000097:blood; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000097:blood; D015470:Leukemia, Myeloid, Acute / Q000097:blood; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000097:blood; D012016:Reference Values; D020112:Rhodamine 123; D012235:Rhodamines / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D014750:Vincristine / Q000633:toxicity
D005456:Fluorescent Dyes; D012235:Rhodamines; D020112:Rhodamine 123; D014750:Vincristine; D006493:Heparin