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Related Experiment Videos

Endostatin induces endothelial cell apoptosis.

M Dhanabal1, R Ramchandran, M J Waterman

  • 1Renal Division, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02215, USA.

The Journal of Biological Chemistry
|April 17, 1999
PubMed
Summary

Endostatin, a collagen fragment, induces apoptosis in endothelial cells by reducing anti-apoptotic proteins Bcl-2 and Bcl-XL. This mechanism explains endostatin

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Area of Science:

  • Biochemistry
  • Molecular Biology
  • Cancer Research

Background:

  • Endostatin, a collagen XVIII fragment, exhibits anti-tumor properties in vivo.
  • Understanding endostatin's mechanism of action is crucial for developing cancer therapies.

Purpose of the Study:

  • To elucidate the molecular mechanisms underlying endostatin's effects on endothelial and nonendothelial cells.
  • To investigate the impact of endostatin on apoptosis pathways in endothelial cells.

Main Methods:

  • Endothelial cells (cow pulmonary artery) were treated with endostatin.
  • Apoptosis was assessed using annexin V-FITC staining, caspase 3 activity assays, and TUNEL assays.
  • Protein levels of Bcl-2, Bcl-XL, and Bax were analyzed via Western blotting.

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Main Results:

  • Endostatin treatment induced significant apoptosis in endothelial cells.
  • A notable decrease in anti-apoptotic proteins Bcl-2 and Bcl-XL was observed.
  • Bax protein levels remained unchanged, and these effects were specific to endothelial cells.

Conclusions:

  • Endostatin selectively induces apoptosis in endothelial cells.
  • The mechanism involves the downregulation of Bcl-2 and Bcl-XL, tipping the balance towards apoptosis.
  • These findings provide critical mechanistic insights into endostatin's anti-angiogenic and anti-tumor effects.