Modulation of nicotinamide adenine dinucleotide and poly(adenosine diphosphoribose) metabolism by calicheamicin γ1 in human HL-60 cells

B. Zhao, S. Konno, J. M. Wu, A. L. Oronsky

Research output: Contribution to journalArticle

Abstract

The mechanism of calicheamicin γ1-mediated cytotoxicity was studied in human promyelocytic HL-60 leukemic cells. Calicheamicin γ1 caused an increase in poly(ADP-ribose) polymerase activity in HL-60 cells parallel to cell death. This effect of the drug correlated with a decrease in intracellular NAD+ level. 3-Aminobenzamide, an inhibitor of poly(ADP-ribosylation), prevented the calicheamicin γ1-triggered cytotoxicity in a dose-dependent manner. Simultaneous with the reversal of cytotoxicity, the addition of 3-aminobenzamide to drug-treated cells also inhibited the increase in poly(ADP-ribosylation) and the reduction in cellular NAD+ content. These results indicate that poly(ADP-ribosylation) activation and the subsquent perturbations in NAD+-dependent metabolic reactions are associated with the cytotoxic properties of the antitumor antibiotic calicheamicin γ1.

Original languageEnglish (US)
Pages (from-to)141-147
Number of pages7
JournalCancer Letters
Volume50
Issue number2
DOIs
StatePublished - Apr 20 1990

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Keywords

  • calicheamicin
  • leukemia
  • poly(ADP-ribosylation)

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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