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Novel anti‐apoptotic effect of Bcl‐2: Prevention of polyamine depletion‐induced cell death
Author(s) -
Holst C. Martina,
Johansson Veronica M.,
Alm Kersti,
Oredsson Stina M.
Publication year - 2008
Publication title -
cell biology international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.932
H-Index - 77
eISSN - 1095-8355
pISSN - 1065-6995
DOI - 10.1016/j.cellbi.2007.08.011
Subject(s) - spermine , polyamine , biology , microbiology and biotechnology , apoptosis , programmed cell death , cytochrome c , mitochondrion , spermidine , biochemistry , enzyme
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.