Abstract
Previous results showed that a novel BH3 mimetic S1 could induce cell death in a wide range of cancer types in vitro through Bax/Bak-dependent apoptosis. We demonstrated that in addition to mitochondrial pathway apoptosis, endoplasmic reticulum (ER) stress-associated apoptosis was also induced by S1. Moreover, S1 can induce autophagy in U251 cells, which may occur through ER stress and disruption of the association of Bcl-2 and Beclin 1. Inhibition of autophagy by the autophagic inhibitors 3-methyladenine (3-MA) or chloroquine (CQ) increased S1-induced apoptosis. In conclusion, autophagy plays an important role in S1-induced U251 cell death.
Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Apoptosis Regulatory Proteins / metabolism*
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Autophagy / drug effects*
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Beclin-1
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Brain Neoplasms / immunology
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Brain Neoplasms / metabolism
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Brain Neoplasms / pathology*
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Cell Line, Tumor
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Endoplasmic Reticulum / drug effects*
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Endoplasmic Reticulum / metabolism
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Glioma / immunology
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Glioma / metabolism
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Glioma / pathology*
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Humans
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In Situ Nick-End Labeling
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Membrane Proteins / metabolism*
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Microscopy, Confocal
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Microscopy, Fluorescence
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Molecular Mimicry*
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Peptide Fragments / pharmacology*
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Proto-Oncogene Proteins / pharmacology*
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Proto-Oncogene Proteins c-bcl-2 / metabolism*
Substances
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Apoptosis Regulatory Proteins
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BECN1 protein, human
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Bax protein (53-86)
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Beclin-1
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Membrane Proteins
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Peptide Fragments
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Proto-Oncogene Proteins
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Proto-Oncogene Proteins c-bcl-2