Modulation of nicotinamide adenine dinucleotide and poly(adenosine diphosphoribose) metabolism by calicheamicin gamma 1 in human HL-60 cells.
The mechanism of calicheamicin gamma 1-mediated cytotoxicity was studied in human promyelocytic HL-60 leukemic cells. Calicheamicin gamma 1 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 gamma 1-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 subsequent perturbations in NAD(+)-dependent metabolic reactions are associated with the cytotoxic properties of the antitumor antibiotic calicheamicin gamma 1.
Zhao
B
B
Department of Biochemistry and Molecular Biology, New York Medical College, Valhalla 10595.
Konno
S
S
Wu
J M
JM
Oronsky
A L
AL
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D000903:Antibiotics, Antineoplastic; D001549:Benzamides / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D004249:DNA Damage; D004273:DNA, Neoplasm / Q000187:drug effects; D053281:Enediynes; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D009243:NAD / Q000378:metabolism*; D009702:Nucleoside Diphosphate Sugars / Q000378:metabolism*; D011064:Poly Adenosine Diphosphate Ribose / Q000378:metabolism*; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism / Q000473:pathology
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D000903:Antibiotics, Antineoplastic; D001549:Benzamides; D004273:DNA, Neoplasm; D053281:Enediynes; D009702:Nucleoside Diphosphate Sugars; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D009243:NAD; C055955:calicheamicin gamma(1)I; D011064:Poly Adenosine Diphosphate Ribose; C025160:3-aminobenzamide; D011065:Poly(ADP-ribose) Polymerases