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

Neoplasma. 2002;49(4):231-6.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / genetics
  • Antineoplastic Agents / metabolism*
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / toxicity
  • Apoptosis / drug effects*
  • Biological Transport
  • Carcinoma / drug therapy
  • Carcinoma / metabolism
  • Daunorubicin / metabolism*
  • Daunorubicin / toxicity
  • Drug Resistance, Multiple
  • Drug Resistance, Neoplasm
  • Drug Synergism
  • Female
  • Fluoresceins / metabolism
  • Fluorescent Dyes / metabolism
  • HL-60 Cells
  • Humans
  • Isoquinolines / metabolism
  • Isoquinolines / pharmacology*
  • Leukemia, Myeloid / drug therapy*
  • Leukemia, Myeloid / metabolism
  • Ligands
  • Mitochondrial Proteins / metabolism
  • Ovarian Neoplasms / drug therapy
  • Ovarian Neoplasms / metabolism
  • Receptors, GABA-A / metabolism
  • Tumor Cells, Cultured

Substances

  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Antineoplastic Agents
  • Fluoresceins
  • Fluorescent Dyes
  • Isoquinolines
  • Ligands
  • Mitochondrial Proteins
  • Receptors, GABA-A
  • calcein AM
  • PK 11195
  • Daunorubicin