Open AccessEndostatin induces autophagy in endothelial cells by modulating Beclin 1 and β‐catenin levels
Author(s) -
Nguyen Tri Minh Bui,
Subramanian Indira V.,
Xiao Xue,
Ghosh Goutam,
Nguyen Phan,
Kelekar Ameeta,
Ramakrishnan S.
Publication year - 2009
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/j.1582-4934.2009.00722.x
Subject(s) - autophagy , endostatin , catenin , microbiology and biotechnology , chemistry , cancer research , biology , vegf receptors , apoptosis , signal transduction , wnt signaling pathway , biochemistry
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.