加利车霉素γ1对人HL-60细胞中烟酰胺腺嘌呤二核苷酸和聚（腺苷二磷酸核糖）代谢的调节作用

Modulation of nicotinamide adenine dinucleotide and poly(adenosine diphosphoribose) metabolism by calicheamicin gamma 1 in human HL-60 cells.

作者信息

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

机构信息

Department of Biochemistry and Molecular Biology, New York Medical College, Valhalla 10595.

出版信息

Cancer Lett. 1990 Apr 20;50(2):141-7. doi: 10.1016/0304-3835(90)90244-r.

DOI:10.1016/0304-3835(90)90244-r

PMID:2109651

Abstract

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.

摘要

在人早幼粒细胞HL-60白血病细胞中研究了刺孢霉素γ1介导的细胞毒性机制。刺孢霉素γ1导致HL-60细胞中多聚（ADP-核糖）聚合酶活性增加，且与细胞死亡平行。该药物的这一作用与细胞内NAD+水平降低相关。3-氨基苯甲酰胺，一种多聚（ADP-核糖基化）抑制剂，以剂量依赖的方式阻止了刺孢霉素γ1引发的细胞毒性。在细胞毒性逆转的同时，向经药物处理的细胞中添加3-氨基苯甲酰胺也抑制了多聚（ADP-核糖基化）的增加以及细胞NAD+含量的降低。这些结果表明，多聚（ADP-核糖基化）激活以及随后NAD(+)依赖性代谢反应的扰动与抗肿瘤抗生素刺孢霉素γ1的细胞毒性特性相关。