Abstract
Beclin 1, identified as a Bcl-2-interacting protein, is known to enhance autophagy. However, the effect of Beclin 1 on apoptotic signaling has remained unclear. Here, we show that overexpression of Beclin 1 in MKN28 human gastric cancer cells augmented cis-diamminedichloroplatinum (CDDP)-induced apoptosis. Conversely, "knockdown" of Beclin 1 by a small inhibitory RNA in MKN 1 cells attenuated this cytotoxicity. Furthermore, not only caspase-3/7 activities, but also caspase-9 activity was increased in Beclin 1 gene transfectants treated with CDDP, and caspase-9 inhibitor completely abolished augmentation of CDDP-induced apoptosis by Beclin 1 as did a caspase-3 inhibitor. Thus, Beclin 1 augments CDDP-induced apoptosis through enhancing caspase-9 activity and functions as a pro-apoptotic molecule.
MeSH terms
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Antineoplastic Agents / toxicity*
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Apoptosis / drug effects*
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Apoptosis Regulatory Proteins
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Beclin-1
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Blotting, Western
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Caspase 3
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Caspase 7
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Caspase 8
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Caspase 9
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Caspases / metabolism*
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Cell Line, Tumor
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Cisplatin / toxicity*
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Enzyme Activation / drug effects
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Enzyme Precursors / metabolism
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Gene Expression Regulation, Neoplastic
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Genes, Tumor Suppressor
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Humans
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Membrane Proteins
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Poly(ADP-ribose) Polymerases / metabolism
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Precipitin Tests
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Proteins / metabolism*
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RNA, Messenger / metabolism
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RNA, Small Interfering / metabolism
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Stomach Neoplasms / genetics
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Stomach Neoplasms / pathology
Substances
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Antineoplastic Agents
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Apoptosis Regulatory Proteins
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BECN1 protein, human
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Beclin-1
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Enzyme Precursors
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Membrane Proteins
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Proteins
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RNA, Messenger
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RNA, Small Interfering
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Poly(ADP-ribose) Polymerases
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CASP3 protein, human
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CASP7 protein, human
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CASP8 protein, human
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CASP9 protein, human
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Caspase 3
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Caspase 7
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Caspase 8
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Caspase 9
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Caspases
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Cisplatin