Staurosporine enhanced benzamide riboside-induced apoptosis in human multidrug-resistant promyelocytic leukemia cells (HL-60/VCR) in vitro

Neoplasma. 1998;45(4):204-9.

Abstract

The inosine monophosphate (IMP) dehydrogenase inhibitor benzamide riboside (BR) induced apoptosis (detected with the aid of flow cytometric identification of cells with sub-G0 DNA content and increased side angle light scatter) equally or slightly more intensively in the multidrug-resistant human promyelocytic leukemia cell line (HL-60/VCR: MDR-1 gene, Pgp positive) in comparison with the parental drug sensitive HL-60 cells. Staurosporine alone induced relatively low level of apoptosis in parental HL-60 cells but higher level (approximately 35%) of apoptosis in multidrug-resistant HL-60/VCR cells after 24 hour induction. The combination of benzamide riboside and staurosporine induced in both drug-sensitive and drug-resistant HL-60 cells a marked proportion of apoptotic cells already after short (6 hour) induction (more than 30% of apoptotic cells).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism
  • Apoptosis / drug effects*
  • DNA Fragmentation
  • Drug Resistance, Multiple*
  • Drug Resistance, Neoplasm*
  • Drug Synergism
  • Enzyme Inhibitors / pharmacology*
  • Flow Cytometry
  • HL-60 Cells / drug effects*
  • Humans
  • IMP Dehydrogenase / antagonists & inhibitors
  • Leukemia, Promyelocytic, Acute / pathology*
  • Neoplasm Proteins / metabolism
  • Nucleosides / pharmacology*
  • Staurosporine / pharmacology*

Substances

  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Enzyme Inhibitors
  • Neoplasm Proteins
  • Nucleosides
  • 3-(1-deoxyribofuranosyl)benzamide
  • IMP Dehydrogenase
  • Staurosporine