Lonidamine causes inhibition of angiogenesis-related endothelial cell functions

Donatella Del Bufalo, Daniela Trisciuoglio, Marco Scarsella, Giulia D'Amati, Antonio Candiloro, Angela Iervolino, Carlo Leonetti, Gabriella Zupi

Research output: Contribution to journalArticle

Abstract

The aim of this study was to assess whether lonidamine (LND) interferes with some steps in angiogenesis progression. We report here, for the first time, that LND inhibited angiogenic-related endothelial cell functions in a dose-dependent manner (1-50 μg/ml). In particular, LND decreased proliferation, migration, invasion, and morphogenesis on matrigel of different endothelial cell lines. Zymographic and Western blot analysis assays showed that LND treatment produced a reduction in the secretion of matrix metalloproteinase-2 and metalloproteinase-9 by endothelial cells. Vessel formation in a matrigel plug was also reduced by LND. The viability, migration, invasion, and matrix metalloproteinase production of different tumor cell lines were not affected by low doses of LND (1-10 μg/ml), whereas 50 μg/ml LND, which corresponds to the dose used in clinical management of tumors, triggered apoptosis both in endothelial and tumor cells. Together, these data demonstrate that LND is a compound that interferes with endothelial cell functions, both at low and high doses. Thus, the effect of LND on endothelial cell functions, previously undescribed, may be a significant contributor to the antitumor effect of LND observed for clinical management of solid tumors.

Original languageEnglish
Pages (from-to)513-522
Number of pages10
JournalNeoplasia (United States)
Volume6
Issue number5
DOIs
Publication statusPublished - Sep 2004

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Keywords

  • Angiogenesis
  • Cancer
  • Endothelial cells
  • Ionidamine
  • Metalloproteinases

ASJC Scopus subject areas

  • Cancer Research

Cite this

Del Bufalo, D., Trisciuoglio, D., Scarsella, M., D'Amati, G., Candiloro, A., Iervolino, A., Leonetti, C., & Zupi, G. (2004). Lonidamine causes inhibition of angiogenesis-related endothelial cell functions. Neoplasia (United States), 6(5), 513-522. https://doi.org/10.1593/neo.04133