A comparative study on the anti-angiogenic effects of DNA-damaging and cytoskeletal-disrupting agents.
The discovery of molecules with anti-angiogenic properties has led to promising new strategies for the treatment of diseases characterized by excessive new vessel growth, such as cancer and haemangioma. We have assessed the effects of DNA-damaging and cytoskeletal-disrupting agents in vitro on several endothelial cell functions. We report that bleomycin, mitomycin C and cytoskeletal-disrupting drugs (2-methoxyestradiol, taxol, vincristine, vinblastine, colchicine, nocodazole, and cytochalasin D) exhibit anti-angiogenic activities of varying potency. Bleomycin and the various cytoskeletal-disrupting drugs inhibited endothelial cell migration, while mitomycin C had a marginal effect. Both DNA-damaging and cytoskeletal-disrupting drugs decreased endothelial cell growth in a dose-dependent manner, and this was accompanied by the induction of apoptosis. The growth inhibitory and apoptotic effects of cytoskeletal-disrupting drugs were the most pronounced. We also show that both classes of drugs inhibited capillary-like tube formation in an assay of in vitro angiogenesis, with cytoskeletal-disrupting agents inhibiting in vitro angiogenesis with greater potency. A targeted approach incorporating several compounds with different mechanisms of action may be useful for the treatment of angiogenesis-dependent diseases such as hemangiomas of infancy.
Mabeta
Peace
P
Department of Physiology, Faculty of Health Sciences, University of Pretoria, Pretoria, South Africa, Peace.mabeta@up.ac.za.
Pepper
Michael S
MS
D000077584:2-Methoxyestradiol; D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001761:Bleomycin / Q000494:pharmacology; D002417:Cattle; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003078:Colchicine / Q000494:pharmacology; D003599:Cytoskeleton / Q000187:drug effects*; D004249:DNA Damage; D053938:DNA Fragmentation / Q000187:drug effects; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology; D016685:Mitomycin / Q000494:pharmacology; D018919:Neovascularization, Physiologic / Q000187:drug effects
D020533:Angiogenesis Inhibitors; D001761:Bleomycin; D004958:Estradiol; D016685:Mitomycin; D000077584:2-Methoxyestradiol; D003078:Colchicine