Endostatin induces autophagy in endothelial cells by modulating Beclin 1 and β-catenin levels

Tri Minh Bui Nguyen, Indira V. Subramanian, Xue Xiao, Goutam Ghosh, Phan Nguyen, Ameeta Kelekar, S. Ramakrishnan

Research output: Contribution to journalArticlepeer-review

76 Scopus citations


Endostatin is a well-characterized endogenous inhibitor of angiogenesis that affects cell proliferation and migration by inhibiting integrin and Wnt-mediated signalling pathways. Here, we show that endothelial cells treated with native and P125A-endostatin activate autophagy. Because autophagy can either be protective or induce programmed cell death, experiments were carried out to understand the signalling pathways leading to autophagy in endothelial cells. P125A-endostatin treatment increased the levels of Beclin 1, a crucial molecule in vesicle nucleation and autophagy. The treatment also reduced the levels of Bcl-2, Bcl-x L and β-catenin; however, progressively increasing amounts of Bcl-2 and Bcl-x L were found to be complexed with Beclin 1. Increased β-catenin and Wnt-mediated signalling reduced Beclin 1 levels and rescued endothelial cells from endostatin-induced autophagy. Finally, knocking down Beclin 1 levels by RNA interference decreased autophagy and accelerated caspase activation in endostatin-treated cells. These studies suggest that endothelial cells may initiate autophagy as a survival response to limit the effects of angiogenesis inhibitors. Thus, interfering with autophagy can potentiate the effects of endostatin by promoting a switch to apoptosis.

Original languageEnglish (US)
Pages (from-to)3687-3698
Number of pages12
JournalJournal of Cellular and Molecular Medicine
Issue number9 B
StatePublished - Sep 2009
Externally publishedYes


  • Angiogenesis
  • Apoptosis
  • Autophagy
  • Bcl-2
  • Bcl-xL
  • Beclin 1
  • Beta-catenin
  • Endostatin
  • Wnt-pathway

ASJC Scopus subject areas

  • Molecular Medicine
  • Cell Biology


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