[Derivative of bleomycin generates less of ROS? Less of fibrosis? Alternative in the development of an efficacy anticancer therapy but less toxic].
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 anti-neoplastic 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.
Brahim
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Laboratoire de Biochimie, Faculté de Médecine de Monastir, UR09/09, Tunisie, France. souhirbrahim@yahoo.fr
Bettaieb
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Kenani
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D000903:Antibiotics, Antineoplastic / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology; D017209:Apoptosis / Q000235:genetics; D001761:Bleomycin / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000502:physiology; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D011658:Pulmonary Fibrosis / Q000139:chemically induced*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013329:Structure-Activity Relationship
D000903:Antibiotics, Antineoplastic; D017382:Reactive Oxygen Species; D001761:Bleomycin; C033284:deglycobleomycin; D020929:Mitogen-Activated Protein Kinase Kinases