PK11195, an isoquinoline carboxamide ligand of the mitochondrial benzodiazepine receptor, increased drug uptake and facilitated drug-induced apoptosis in human multidrug-resistant leukemia cells in vitro.
The isoquinoline peripheral benzodiazepine receptor ligand PK11195 increased drug (daunomycin)- and fluorochrome (calcein-AM) uptake and induced apoptosis detected by flow cytometry (FCM) technique, DNA electrophoretic analysis and poly(ADP-ribose) polymerase (PARP) cleavage in human multidrug-resistant myeloid leukemia (BL-60/VCR) and ovarian carcinoma (A2780/ADR) cells in vitro. The position of PK11195 with respect to drug-resistance modulator (DRM) efficiency, compared to the reference DRMs with the aid of FCM technique, was as follows: PSC833 > verapamil > PK11195 > vincristine. Our data show up to now not indicated observation that PK11195 possesses multidrug resistance modulating activity.
Jakubikova
J
J
Cancer Research Institute, Slovak Academy of Sciences, 83391 Bratislava, Slovakia, Republic. exonsedl@savba.sk
Duraj
J
J
Hunakova
L
L
Chorvath
B
B
Sedlak
J
J
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics; D000970:Antineoplastic Agents / Q000378:metabolism* / Q000494:pharmacology* / Q000633:toxicity; D017209:Apoptosis / Q000187:drug effects*; D001692:Biological Transport; D002277:Carcinoma / Q000188:drug therapy / Q000378:metabolism; D003630:Daunorubicin / Q000378:metabolism* / Q000633:toxicity; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D004357:Drug Synergism; D005260:Female; D005452:Fluoresceins / Q000378:metabolism; D005456:Fluorescent Dyes / Q000378:metabolism; D018922:HL-60 Cells; D006801:Humans; D007546:Isoquinolines / Q000378:metabolism / Q000494:pharmacology*; D007951:Leukemia, Myeloid / Q000188:drug therapy* / Q000378:metabolism; D008024:Ligands; D024101:Mitochondrial Proteins / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000378:metabolism; D011963:Receptors, GABA-A / Q000378:metabolism; D014407:Tumor Cells, Cultured
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents; D005452:Fluoresceins; D005456:Fluorescent Dyes; D007546:Isoquinolines; D008024:Ligands; D024101:Mitochondrial Proteins; D011963:Receptors, GABA-A; C085925:calcein AM; C037850:PK 11195; D003630:Daunorubicin