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
Externally publishedYes

Fingerprint

Adenosine Diphosphate Ribose
HL-60 Cells
NAD
Adenosine Diphosphate
Poly(ADP-ribose) Polymerases
Pharmaceutical Preparations
Cell Death
Anti-Bacterial Agents
3-aminobenzamide

Keywords

  • calicheamicin
  • leukemia
  • poly(ADP-ribosylation)

ASJC Scopus subject areas

  • Cancer Research
  • Molecular Biology
  • Oncology

Cite this

Modulation of nicotinamide adenine dinucleotide and poly(adenosine diphosphoribose) metabolism by calicheamicin γ1 in human HL-60 cells. / Zhao, B.; Konno, S.; Wu, J. M.; Oronsky, A. L.

In: Cancer Letters, Vol. 50, No. 2, 20.04.1990, p. 141-147.

Research output: Contribution to journalArticle

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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.",
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AU - Oronsky, A. L.

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N2 - 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.

AB - 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.

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