Antiangiogenesis is produced by nontoxic doses of vinblastine

Angelo Vacca, Monica Iurlaro, Domenico Ribatti, Monica Minischetti, Beatrice Nico, Roberto Ria, Antonio Pellegrino, Franco Dammacco

Research output: Contribution to journalArticle

Abstract

The effects of vinblastine (VBL) on endothelial cell functions involved in angiogenesis, namely proliferation, chemotaxis, spreading on fibronectin (FN), secretion of matrix-metalloproteinase-2 (MMP-2) and MMP-9, and morphogenesis on Matrigel were tested in vitro, whereas its effects on angiogenesis were studied in vivo by using the chick embryo chorioallantoic membrane (CAM) model. In vitro, at noncytotoxic doses (0.1, 0.25, 0.5, 0.75, and 1 pmol/L), VBL impacted all these functions, except secretion of MMPs, in a dose-dependent fashion. By contrast, proliferation of other primary cells such as fibroblasts and lymphoid tumor cells was not impacted. In vivo, VBL at 0.5, 0.75, and 1 pmol/L again displayed a dose-dependent antiangiogenic activity. Lack of cytotoxicity in vitro and in vivo was shown both morphologically, and also because the antiangiogenic effects were rapidly abolished when VBL was removed. Apoptosis was not induced. At the ultrastructural level, impairment of cell functions in vitro was associated with thin disturbance of the cytoskeleton, in the form of slight depolymerization and accumulation of microfilaments, which was equally reversible. Results suggest that VBL has an antiangiogenic component at very low, noncytotoxic doses, and that antiangiogenesis by VBL could be used to treat a wide spectrum of angiogenesis-dependent diseases, including certain chronic inflammatory diseases, Kaposi's sarcoma, and cancer.

Original languageEnglish
Pages (from-to)4143-4155
Number of pages13
JournalBlood
Volume94
Issue number12
Publication statusPublished - Dec 15 1999

ASJC Scopus subject areas

  • Hematology

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    Vacca, A., Iurlaro, M., Ribatti, D., Minischetti, M., Nico, B., Ria, R., Pellegrino, A., & Dammacco, F. (1999). Antiangiogenesis is produced by nontoxic doses of vinblastine. Blood, 94(12), 4143-4155.