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. Endostati n treatment of cow pulmonary artery endothelial cells caused apoptosis, as demonstrated by three methods, annexin V-fluorescein isothiocyanate stainin g, caspase 3, and terminal deoxynucleotidyl transferase-mediated dUTP nick- end-labeling assay. Moreover, addition of endostatin led to a marked reduct ion of the Bcl-2 and Bcl-X-L anti-apoptotic protein, whereas Bar protein le vels were unaffected. These effects were not seen in several nonendothelial cells. Collectively, these findings provide important mechanistic insight into endostatin action.