Novel anti-apoptotic effect of Bcl-2: prevention of polyamine depletion-induced cell death.
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.
Holst
C Martina
CM
Department of Cell and Organism Biology, Lund University, Helgonavägen 3B, SE-223 62 Lund, Sweden. martina.holst@cob.lu.se
Johansson
Veronica M
VM
Alm
Kersti
K
Oredsson
Stina M
SM
D000123:Acetyltransferases / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects*; D051033:Apoptosis Inducing Factor / Q000378:metabolism; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D001943:Breast Neoplasms / Q000378:metabolism*; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D045304:Cytochromes c / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000378:metabolism; D009363:Neoplasm Proteins / Q000378:metabolism; D011073:Polyamines / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis / Q000502:physiology*; D013096:Spermine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000077022:Survivin; D014162:Transfection; D051028:bcl-2-Associated X Protein / Q000378:metabolism; D000099228:Diamine N-Acetyltransferase
D000123:Acetyltransferases; D051033:Apoptosis Inducing Factor; D051017:Apoptosis Regulatory Proteins; D053148:Caspase 3; D045304:Cytochromes c; D051034:Inhibitor of Apoptosis Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008869:Microtubule-Associated Proteins; D024101:Mitochondrial Proteins; D009363:Neoplasm Proteins; D011073:Polyamines; D019253:Proto-Oncogene Proteins c-bcl-2; D013096:Spermine; D000077022:Survivin; D051028:bcl-2-Associated X Protein; D000099228:Diamine N-Acetyltransferase; C107489:BIRC5 protein, human; C412403:DIABLO protein, human; C059685:N(1),N(11)-diethylnorspermine