title: Lonidamine causes inhibition of angiogenesis-related endothelial cell functions.
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 microg/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 microg/ml), whereas 50 microg/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.
authors.affiliation: Experimental Chemotherapy Laboratory, Regina Elena Cancer Institute, Rome, Italy. delbufalo@ifo.it
authors.forename: Donatella
authors.initials: D
authors.lastname: Del Bufalo
authors.forename: Daniela
authors.initials: D
authors.lastname: Trisciuoglio
authors.forename: Marco
authors.initials: M
authors.lastname: Scarsella
authors.forename: Giulia
authors.initials: G
authors.lastname: D'Amati
authors.forename: Antonio
authors.initials: A
authors.lastname: Candiloro
authors.forename: Angela
authors.initials: A
authors.lastname: Iervolino
authors.forename: Carlo
authors.initials: C
authors.lastname: Leonetti
authors.forename: Gabriella
authors.initials: G
authors.lastname: Zupi
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D002454:Cell Differentiation / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003094:Collagen / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D004730:Endothelium, Vascular / Q000187:drug effects*; D006801:Humans; D007191:Indazoles / Q000494:pharmacology*; D007797:Laminin / Q000008:administration & dosage; D020778:Matrix Metalloproteinase 2 / Q000032:analysis / Q000096:biosynthesis; D020780:Matrix Metalloproteinase 9 / Q000032:analysis / Q000096:biosynthesis; D051379:Mice; D018919:Neovascularization, Physiologic / Q000187:drug effects; D011509:Proteoglycans / Q000008:administration & dosage; D014471:Umbilical Veins / Q000166:cytology; D042461:Vascular Endothelial Growth Factor A / Q000008:administration & dosage / Q000494:pharmacology
chemical_list: D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D004338:Drug Combinations; D007191:Indazoles; D007797:Laminin; D011509:Proteoglycans; D042461:Vascular Endothelial Growth Factor A; C059485:matrigel; D003094:Collagen; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; C016371:lonidamine