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

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.

Diagnosis and Management of Infantile Hemangioma

“…It induces endothelial cell apoptosis and is also a potent inhibitor of endothelial cell growth, migration, and in vitro capillary-like tube formation. 248 Given that endothelial cells also possess a high tubulin content, a biological rationale for IH sensitivity to vincristine exists. 249 Most reports on the efficacy of vincristine address the treatment of patients with vascular lesions that were not true IHs but rather KHE or TAs associated with KMP.…”

Advances in Techniques for Probing Mechanoregulation of Tissue Morphogenesis

“…38 In addition, nocodazole exhibits anti-angiogenic effects in vitro along with potent inhibitory effects on endothelial growth. 39 Taxol (paclitaxel), an agent that stabilizes microtubules, facilitates microtubule polymerization and increases cell stiffness and viscosity. 40 Taxol has been actively investigated for its anti-angiogenic effects both in vitro and in vivo.…”

Hemangiomas - current therapeutic strategies

“…This is corroborated by the observation that bleomycin inhibits growth factor-induced endothelial cell invasion, endothelial cell growth and migration, and also induces endothelial cell apoptosis (Mabeta and Pepper, 2009).…”

“…In a study using the CAM assay, vincristine had an inhibitory effect on vascularisation. The drug is also a potent inhibitor of endothelial cell growth, migration and in vitro capillary-like tube formation, and induces endothelial cell apoptosis (Mabeta and Pepper, 2009). Only a few studies have reported on the use of vincristine for the treatment of IH.…”