Abstract
The spermine analogue N(1),N(11)-diethylnorspermine (DENSPM) efficiently depletes the polyamine pools in the breast cancer cell line L56Br-C1 and induces apoptotic cell death via the mitochondrial pathway. In this study, we have over-expressed the anti-apoptotic protein Bcl-2 in L56Br-C1 cells and investigated the effect of DENSPM treatment. DENSPM-induced cell death was significantly reduced in Bcl-2 over-expressing cells. Bcl-2 over-expression reduced DENSPM-induced release of the pro-apoptotic proteins AIF, cytochrome c, and Smac/DIABLO from the mitochondria. Bcl-2 over-expression reduced the DENSPM-induced activation of caspase-3. Bcl-2 over-expression also prevented DENSPM-induced Bax cleavage and reduction of Bcl-X(L) and survivin levels. The DENSPM-induced activation of the polyamine catabolic enzyme spermidine/spermine N(1)-acetyltransferase was reduced by Bcl-2 over-expression, partly preventing polyamine depletion. Thus, Bcl-2 over-expression prevented a number of DENSPM-induced apoptotic effects.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Acetyltransferases / metabolism
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Apoptosis / drug effects*
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Apoptosis Inducing Factor / metabolism
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Apoptosis Regulatory Proteins / metabolism
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Breast Neoplasms / metabolism*
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Caspase 3 / metabolism
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Cell Line, Tumor
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Cytochromes c / metabolism
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Gene Expression Regulation, Neoplastic
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Humans
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Inhibitor of Apoptosis Proteins
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Intracellular Signaling Peptides and Proteins / metabolism
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Microtubule-Associated Proteins / metabolism
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Mitochondrial Proteins / metabolism
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Neoplasm Proteins / metabolism
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Polyamines / metabolism
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Proto-Oncogene Proteins c-bcl-2 / biosynthesis
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Proto-Oncogene Proteins c-bcl-2 / physiology*
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Spermine / analogs & derivatives*
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Spermine / pharmacology
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Survivin
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Transfection
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bcl-2-Associated X Protein / metabolism
Substances
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Apoptosis Inducing Factor
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Apoptosis Regulatory Proteins
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BIRC5 protein, human
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DIABLO protein, human
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Inhibitor of Apoptosis Proteins
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Intracellular Signaling Peptides and Proteins
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Microtubule-Associated Proteins
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Mitochondrial Proteins
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Neoplasm Proteins
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Polyamines
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Proto-Oncogene Proteins c-bcl-2
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Survivin
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bcl-2-Associated X Protein
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N(1),N(11)-diethylnorspermine
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Spermine
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Cytochromes c
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Acetyltransferases
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diamine N-acetyltransferase
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Caspase 3