Cytotoxic effect of free bleomycin A5-iron (II) complex and its conjugates with concanavalin A, insulin and calcitonin on mouse thymocytes.
The possibility of using the antibiotic bleomycin as a part of a hybrid molecule consisting of a targeting fragment and a generator of reactive oxygen species has been investigated. The bleomycin-iron (II) complex was shown to destroy the plasma membrane of thymocytes by producing reactive oxygen species. Antioxidants protected the cells from destruction thus pointing to its free-radical mechanism. The protective effects of catalase and superoxide dismutase indicate that superoxide radical and hydrogen peroxide being formed during autooxidation of the complex are involved in cell damage. The covalent binding of bleomycin to targeting molecules (concanavalin A, insulin, and calcitonin) enhanced the ability of the bleomycin-iron (II) complex to destroy the plasma membrane of thymocytes.
Matkhanov
I E
IE
Institute of Biomedical Chemistry, Russian Academy of Medical Sciences, Moscow.
Galanova YuV
Voschinnikov
E I
EI
Archakov
A I
AI
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001562:Benzimidazoles / Q000378:metabolism; D001761:Bleomycin / Q000494:pharmacology* / Q000031:analogs & derivatives; D002116:Calcitonin / Q000187:drug effects / Q000494:pharmacology; D002374:Catalase / Q000494:pharmacology; D002462:Cell Membrane / Q000187:drug effects* / Q000378:metabolism; D003208:Concanavalin A / Q000031:analogs & derivatives / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D005296:Ferrous Compounds / Q000494:pharmacology*; D005609:Free Radicals; D007328:Insulin / Q000031:analogs & derivatives / Q000494:pharmacology; D015227:Lipid Peroxidation; D051379:Mice; D008808:Mice, Inbred CBA; D009245:NADH Dehydrogenase / Q000032:analysis; D010100:Oxygen / Q000378:metabolism; D013482:Superoxide Dismutase / Q000494:pharmacology; D013601:T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology / Q000187:drug effects*
D000975:Antioxidants; D001562:Benzimidazoles; D005296:Ferrous Compounds; D005609:Free Radicals; D007328:Insulin; D003208:Concanavalin A; D001761:Bleomycin; C025703:bleomycetin; D002116:Calcitonin; D002374:Catalase; D013482:Superoxide Dismutase; D009245:NADH Dehydrogenase; C017807:bisbenzimide ethoxide trihydrochloride; D010100:Oxygen