Novel anti-apoptotic effect of Bcl-2: prevention of polyamine depletion-induced cell death.

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.

• Authors: C Martina Holst, Veronica M Johansson, Kersti Alm, Stina M Oredsson
• Journal: Cell biology international (Cell Biol Int) Vol. 32 Issue 1 Pg. 66-74 (Jan 2008) ISSN: 1065-6995 [Print] England
• PMID: 17920946 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Apoptosis Inducing Factor
• Apoptosis Regulatory Proteins
• BIRC5 protein, human
• DIABLO protein, human
• Inhibitor of Apoptosis Proteins
• Intracellular Signaling Peptides and Proteins
• Microtubule-Associated Proteins
• Mitochondrial Proteins
• Neoplasm Proteins
• Polyamines
• Proto-Oncogene Proteins c-bcl-2
• Survivin
• bcl-2-Associated X Protein
• N(1),N(11)-diethylnorspermine
• Spermine
• Cytochromes c
• Acetyltransferases
• diamine N-acetyltransferase
• Caspase 3

Topics

• Acetyltransferases (metabolism)
• Apoptosis (drug effects)
• Apoptosis Inducing Factor (metabolism)
• Apoptosis Regulatory Proteins (metabolism)
• Breast Neoplasms (metabolism)
• Caspase 3 (metabolism)
• Cell Line, Tumor
• Cytochromes c (metabolism)
• Gene Expression Regulation, Neoplastic
• Humans
• Inhibitor of Apoptosis Proteins
• Intracellular Signaling Peptides and Proteins (metabolism)
• Microtubule-Associated Proteins (metabolism)
• Mitochondrial Proteins (metabolism)
• Neoplasm Proteins (metabolism)
• Polyamines (metabolism)
• Proto-Oncogene Proteins c-bcl-2 (biosynthesis, physiology)
• Spermine (analogs & derivatives, pharmacology)
• Survivin
• Transfection
• bcl-2-Associated X Protein (metabolism)