Derivative of bleomycin generates less of ROS? Less of fibrosis? Alternative in the development of an efficacy anticancer therapy but less toxic

被引:1
作者
Brahim, S. [1 ]
Bettaieb, A. [2 ,3 ]
Kenani, A. [1 ]
机构
[1] Fac Med Monastir, Biochim Lab, Tunis, Tunisia
[2] Univ Bourgogne, INSERM, U866, F-21000 Dijon, France
[3] Ecole Prat Hautes Etud, F-21000 Dijon, France
关键词
bleomycin; deglycobleomycin; cytotoxicity; apoptosis; ROS; pulmonary fibrosis; JUN NH2-TERMINAL KINASE; LUNG EPITHELIAL-CELLS; PULMONARY TOXICITY; DEATH PATHWAY; APOPTOSIS; DNA; CARCINOMA; CHEMOTHERAPY; ACTIVATION; CISPLATIN;
D O I
10.1684/bdc.2009.1034
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Deglycobleomycin (DBLM), the aglycon of the glycopeptide antitumor drug bleomycin (BLM), was first used since 1980 during comparative studies between BLM and DBLM in order to elucidate the role of the sugar component in the mechanism of action of BLM. In fact, the deglycosylation of BLM reduce the toxicity of this molecule and fails to produce reactive oxygen species, responsible for pulmonary fibrosis, and for antineoplastic activity of BLM. This causes toxic DNA lesions and ultimately leads to cell death. The therapeutic use of BLM is limited by a dose-dependent lung toxicity that eventually leads to fibrosis. Testing BLM-derivative molecules and defining their molecular mechanisms involved in tumor cell death may help to design new therapeutic approach with limited toxicity profile while maintaining anti-tumoral properties. The present review was undertaken to determine the effect of carbohydrate moiety in the mechanism of BLM induced cytotoxicity behind a comparative studies between BLM and DBLM. triangle
引用
收藏
页码:527 / 534
页数:8
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