思文霉素对胞外DNA拓扑异构酶介导产生的断裂和松驰反应的影响

思文霉素对胞外DNA拓扑异构酶介导产生的断裂和松驰反应的影响

彭瑶, 包定元, 王龙贵, 刘晓梅, 籍秀娟

1. 华西医科大学, 成都 610041;
2. 中国医学科学院药物研究所, 北京 100050

收稿日期:1993-01-03 修回日期:1994-05-26 出版日期:1994-12-15 发布日期:1994-12-15

Effects of Siwenmycin on DNA Topoisomerases Mediated Strand Cleavage and Relaxation in Vitro

Yao Peng, Ding-Yuan Bao, Long-Gui Wang, Xiao-Mei Liu, Xiu-Juan Ji

1. West China University of Medical Sciences, Chengdu 610041;
2. Institute of Materia Medica, Chinese Academy of Medical Sciences, Beijing 100050

Received:1993-01-03 Revised:1994-05-26 Online:1994-12-15 Published:1994-12-15

摘要/Abstract

摘要： 思文霉素(Siwenmycin)是最先从我国土壤中的链霉菌培养物中提取的一个新型蒽环类抗生素。研究表明该药是DNA拓扑异构酶抑制剂。以ATP依赖性pBR322DNA断裂松弛反应, 观察思文霉素对从哺乳动物细胞中提取的DNA拓扑异构酶II活性的抑制作用后发现该药对此酶的最大抑制浓度为25mmol/L。用思文霉素处理Bel7402细胞后, 从中提取的DNA拓扑异构酶II所介导的DNA断裂松驰反应活性比对照组增加5倍。研究还发现, 思文霉素可抑制胞外DNA拓扑异构酶I活性。碱性洗脱实验证明该药可引起DNA单链断裂。

关键词: 蒽环类抗生素, 思文霉素, DNA拓扑异构酶, 肿瘤靶点

Abstract: Siwenmycin, a novel anthracycline antibiotic, was first isolated from a culture of streptomyces galilaeus var. siwenesis of a piece of chinese Siwenmycin inhibited purified mammalian DNA topoisomerase II with a maximal inhibitory concentration of 25 μmol/L as assessed by the ATP-dependent relaxation of supercoiled pBR322 DNA. DNA cleavage aI1d relaxing reactions induced by DNA topoisomerase II obtained from Bel 7402 cells treated with siwenmycin, were increased by 5-fold comparing with control. In addition, siwenmycin also inhibited the catalytic activity of DNA topoisomerases I and induced single-strand DNA breakage in vitro. The results showed that topoisomerases I and II are the cellular targets of siwenmycin, the study of these targets will provide a rational basis for the structural design of aclacinomycin analogues.

Key words: Anthracycline antibiotics, Siwenmycin, DNA topoisomerases, Tumor targets

Supporting:

彭瑶, 包定元, 王龙贵, 刘晓梅, 籍秀娟. 思文霉素对胞外DNA拓扑异构酶介导产生的断裂和松驰反应的影响[J]. .

Yao Peng, Ding-Yuan Bao, Long-Gui Wang, Xiao-Mei Liu, Xiu-Juan Ji. Effects of Siwenmycin on DNA Topoisomerases Mediated Strand Cleavage and Relaxation in Vitro[J]. .