Chemosensitizing interactions of clofazimine and B669 with human K562 erythroleukaemia cells with varying levels of expression of P-glycoprotein.
Differential expression of a permeability glycoprotein (P-gp) in human myeloleukaemia K562 cells grown in the presence of the anti-cancer drug, doxorubicin, gave rise to subclones with varying degrees of resistance to other anti-tumour drugs such as vinblastine and daunorubicin. Subclones K562/MMB, MMG and MMF were produced from the parental (K562/P) cell line via limiting dilution and their MDR nature confirmed with flow cytometry using an MRK 16 monoclonal antibody directed at a surface epitope of the P-gp pump. The pattern of increasing P-gp expression in the series K562/P, MMF, MMG and MMB was paralleled by increasing resistance to vinblastine and daunorubicin. When the subclones were pre-incubated with the chemosensitizing drugs clofazimine and B669, a pattern of increasing reversal of resistance to vinblastine and daunorubicin was seen in the series K562/P, MMF, MMG and MMB.
Myer
M S
MS
Department of Immunology, University of Pretoria, South Africa.
Van Rensburg
C E
CE
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000096:biosynthesis / Q000378:metabolism*; D000970:Antineoplastic Agents / Q000494:pharmacology; D000972:Antineoplastic Agents, Phytogenic / Q000493:pharmacokinetics; D002991:Clofazimine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D004347:Drug Interactions; D018432:Drug Resistance, Multiple; D004354:Drug Screening Assays, Antitumor; D004976:Ethacrynic Acid / Q000494:pharmacology; D005434:Flow Cytometry; D019833:Genistein; D006801:Humans; D007529:Isoflavones / Q000494:pharmacology; D004915:Leukemia, Erythroblastic, Acute / Q000188:drug therapy* / Q000378:metabolism*; D014316:Tritium; D014407:Tumor Cells, Cultured / Q000187:drug effects; D014747:Vinblastine / Q000493:pharmacokinetics
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents; D000972:Antineoplastic Agents, Phytogenic; D007529:Isoflavones; D014316:Tritium; D014747:Vinblastine; C030428:B 669; D002991:Clofazimine; D019833:Genistein; D004976:Ethacrynic Acid