CPT-11-induced cell death in leukemic cells is not affected by the MDR phenotype

Leuk Res. 2003 Mar;27(3):243-51. doi: 10.1016/s0145-2126(02)00094-2.

Abstract

CPT-11 is a topoisomerase I (Topo I) inhibitor which was initially described as active in multi-drug resistance (MDR) tumors. The MDR phenomenon is characterized by the overexpression of efflux pumps which are able to extrude a range of drugs non-related chemical or functionally. In this work, we treated leukemic cells with CPT-11 300 microM at 24h and compared its cytotoxicity with the activity of efflux pumps and with cell cycle phase. Our findings show that CPT-11 has a potent anti-tumor activity in leukemic cells regardless MDR phenotype and the cell cycle phase, suggesting new avenues to be explored in leukemia treatment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / physiology
  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Blood Cells / pathology
  • Bone Marrow Cells / pathology
  • Camptothecin / analogs & derivatives*
  • Camptothecin / pharmacology*
  • Cell Death / drug effects
  • Drug Resistance, Multiple / genetics*
  • Female
  • Humans
  • Interphase
  • Irinotecan
  • Leukemia / drug therapy
  • Leukemia / pathology*
  • Leukocytes, Mononuclear / drug effects
  • Leukocytes, Mononuclear / pathology
  • Male
  • Middle Aged
  • Multidrug Resistance-Associated Proteins / physiology
  • Phenotype
  • Rhodamine 123
  • Topoisomerase I Inhibitors
  • Tumor Cells, Cultured

Substances

  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Antineoplastic Agents, Phytogenic
  • Multidrug Resistance-Associated Proteins
  • Topoisomerase I Inhibitors
  • Rhodamine 123
  • Irinotecan
  • Camptothecin