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

doi:10.1016/0304-3835(90)90244-R

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

School of Medicine

Research output: Contribution to journal › Article › peer-review

24 Scopus citations

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 language	English (US)
Pages (from-to)	141-147
Number of pages	7
Journal	Cancer Letters
Volume	50
Issue number	2
DOIs	https://doi.org/10.1016/0304-3835(90)90244-R
State	Published - Apr 20 1990

Keywords

calicheamicin
leukemia
poly(ADP-ribosylation)

ASJC Scopus subject areas

Oncology
Cancer Research

Access to Document

10.1016/0304-3835(90)90244-R

Cite this

@article{bc9cfca49beb4d72a3a5b9e281de3341,

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

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.",

keywords = "calicheamicin, leukemia, poly(ADP-ribosylation)",

author = "B. Zhao and S. Konno and Wu, {J. M.} and Oronsky, {A. L.}",

note = "Funding Information: This research was supported by a grant from Lederle Laboratories. We thank Ms. Maria Lannon for typing the manuscript. Mr. Douglas Issacs assisted with cell counts for some of the experimentsr eported here.",

year = "1990",

month = apr,

day = "20",

doi = "10.1016/0304-3835(90)90244-R",

language = "English (US)",

volume = "50",

pages = "141--147",

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T1 - Modulation of nicotinamide adenine dinucleotide and poly(adenosine diphosphoribose) metabolism by calicheamicin γ1 in human HL-60 cells

AU - Zhao, B.

AU - Konno, S.

AU - Wu, J. M.

AU - Oronsky, A. L.

N1 - Funding Information: This research was supported by a grant from Lederle Laboratories. We thank Ms. Maria Lannon for typing the manuscript. Mr. Douglas Issacs assisted with cell counts for some of the experimentsr eported here.

PY - 1990/4/20

Y1 - 1990/4/20

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.

KW - calicheamicin

KW - leukemia

KW - poly(ADP-ribosylation)

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