Endostatin Induces Endothelial Cell Apoptosis

Endostatin, a carboxyl-terminal fragment of collagen XVIII, has been shown to regress tumors in mice. In this study, we have analyzed the mechanism of endostatin action on endothelial cells and nonendothelial cells. Endostatin treatment of cow pulmonary artery endothelial cells caused apoptosis, as...

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Bibliographic Details
Published in:The Journal of biological chemistry 1999-04, Vol.274 (17), p.11721-11726
Main Authors: Dhanabal, M, Ramchandran, R, Waterman, M J, Lu, H, Knebelmann, B, Segal, M, Sukhatme, V P
Format: Article
Language:English
Subjects:
Animals
Apoptosis - drug effects
Biological Transport
Cattle
Cell Membrane - metabolism
Cell Nucleus - drug effects
Cell Nucleus - metabolism
Collagen - pharmacology
Collagen Type XVIII
Endostatins
Endothelium, Vascular - cytology
Endothelium, Vascular - drug effects
Endothelium, Vascular - metabolism
In Situ Nick-End Labeling
Mice
Peptide Fragments - pharmacology
Phosphatidylserines - metabolism
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Summary:Endostatin, a carboxyl-terminal fragment of collagen XVIII, has been shown to regress tumors in mice. In this study, we have analyzed the mechanism of endostatin action on endothelial cells and nonendothelial cells. Endostatin treatment of cow pulmonary artery endothelial cells caused apoptosis, as demonstrated by three methods, annexin V-fluorescein isothiocyanate staining, caspase 3, and terminal deoxynucleotidyl transferase-mediated dUTP nick-end-labeling assay. Moreover, addition of endostatin led to a marked reduction of the Bcl-2 and Bcl-X L anti-apoptotic protein, whereas Bax protein levels were unaffected. These effects were not seen in several nonendothelial cells. Collectively, these findings provide important mechanistic insight into endostatin action.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.274.17.11721