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 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-XL 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.
Dhanabal
M
M
Renal Division, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02215, USA.
Ramchandran
R
R
Waterman
M J
MJ
Lu
H
H
Knebelmann
B
B
Segal
M
M
Sukhatme
V P
VP
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001692:Biological Transport; D002417:Cattle; D002462:Cell Membrane / Q000378:metabolism; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D003094:Collagen / Q000494:pharmacology*; D043170:Collagen Type XVIII; D043169:Endostatins; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D020287:In Situ Nick-End Labeling; D051379:Mice; D010446:Peptide Fragments / Q000494:pharmacology*; D010718:Phosphatidylserines / Q000378:metabolism
D043170:Collagen Type XVIII; D043169:Endostatins; D010446:Peptide Fragments; D010718:Phosphatidylserines; D003094:Collagen