Idarubicin and idarubicinol are less affected by topoisomerase II-related multidrug resistance than is daunorubicin

Leuk Res. 1998 Jul;22(7):625-9. doi: 10.1016/s0145-2126(98)00060-5.

Abstract

We investigated the cytotoxicity and cellular pharmacology of idarubicin (IDA), idarubicinol (IDAol) and daunorubicin (DNR) in K562/VP-H2 cells, which show topoisomerase II-related multidrug resistance but do not overexpress P-glycoprotein. K562/VP-H2 cells were less resistant to IDA and IDAol than to DNR. There was no significant difference in the accumulation of each drug between K562 and K562/VP-H2 cells. The cleavage of DNA induced by each drug was decreased in K562/VP-H2 cells, however, the decrease in cleavage in K562/VP-H2 cells was less with IDA and IDAol than with DNR. These results suggest that IDA and IDAol have more cytotoxic potency than DNR in topoisomerase II-related multidrug-resistant leukemia cells.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Cell Division / drug effects
  • Cell Extracts / chemistry
  • Cell Survival / drug effects
  • Cytotoxins / pharmacology
  • DNA Topoisomerases, Type II / physiology*
  • Daunorubicin / analogs & derivatives*
  • Daunorubicin / analysis
  • Daunorubicin / pharmacology*
  • Drug Resistance, Neoplasm / physiology
  • Drug Screening Assays, Antitumor
  • Humans
  • Idarubicin / analysis
  • Idarubicin / pharmacology*
  • Trypan Blue
  • Tumor Cells, Cultured / cytology
  • Tumor Cells, Cultured / drug effects
  • Tumor Cells, Cultured / enzymology

Substances

  • Antineoplastic Agents
  • Cell Extracts
  • Cytotoxins
  • idarubicinol
  • DNA Topoisomerases, Type II
  • Trypan Blue
  • Idarubicin
  • Daunorubicin