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A comparative study on the anti-angiogenic effects of DNA-damaging and cytoskeletal-disrupting agents

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Abstract

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.

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Acknowledgments

We would like to thank Corinne Di Sanza and Mireille Quayzin for excellent technical assistance. We also thank Prof Piet Becker, Biostats Unit, Medical Research Council, for assistance with statistical analysis. This work was funded by the Swiss National Science Foundation (grant no. 3100-064037.00 to MSP) and the National Research Foundation.

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Authors and Affiliations

  1. Department of Physiology, Faculty of Health Sciences, University of Pretoria, Pretoria, South Africa

    Peace Mabeta

  2. Department of Immunology, Faculty of Health Sciences, University of Pretoria, P.O. Box 2034, Pretoria, 0001, South Africa

    Michael S. Pepper

  3. Département de Médecine Génétique et Développement, University Medical Centre, Geneva, Switzerland

    Michael S. Pepper

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  1. Peace Mabeta
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  2. Michael S. Pepper
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Correspondence to Michael S. Pepper.

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Mabeta, P., Pepper, M.S. A comparative study on the anti-angiogenic effects of DNA-damaging and cytoskeletal-disrupting agents. Angiogenesis 12, 81–90 (2009). https://doi.org/10.1007/s10456-009-9134-8

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  • DOI: https://doi.org/10.1007/s10456-009-9134-8

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