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

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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)
Issue number5
Publication statusPublished - Sep 2004



  • 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