TY - JOUR
T1 - Lonidamine causes inhibition of angiogenesis-related endothelial cell functions
AU - Del Bufalo, Donatella
AU - Trisciuoglio, Daniela
AU - Scarsella, Marco
AU - D'Amati, Giulia
AU - Candiloro, Antonio
AU - Iervolino, Angela
AU - Leonetti, Carlo
AU - Zupi, Gabriella
PY - 2004/9
Y1 - 2004/9
N2 - 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.
AB - 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.
KW - Angiogenesis
KW - Cancer
KW - Endothelial cells
KW - Ionidamine
KW - Metalloproteinases
UR - http://www.scopus.com/inward/record.url?scp=6944226324&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=6944226324&partnerID=8YFLogxK
U2 - 10.1593/neo.04133
DO - 10.1593/neo.04133
M3 - Article
C2 - 15548359
AN - SCOPUS:6944226324
VL - 6
SP - 513
EP - 522
JO - Neoplasia
JF - Neoplasia
SN - 1522-8002
IS - 5
ER -