Premium
Differential regulation of apoptosis in AK‐5 tumor cells by the proto‐oncogene Bcl‐2: presence of Bcl‐2 dependent and independent pathways
Author(s) -
Anjum Rana,
Khar Ashok
Publication year - 2001
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(01)02543-1
Subject(s) - apoptosis , programmed cell death , mitochondrion , microbiology and biotechnology , cytochrome c , biology , cytosol , ceramide , cell culture , inducer , cancer research , biochemistry , enzyme , gene , genetics
The anti‐apoptotic protein Bcl‐2 functions as a crucial negative regulator of apoptosis. Bcl‐2 has been shown to prevent the efflux of apoptogenic factors from mitochondria to cytosol, thus inhibiting cell death. Here, we show the susceptibility of a spontaneously regressing, rat histiocytic tumor cell line, AK‐5, to the apoptotic effects of diverse stimuli and the ability of Bcl‐2 overexpression to block cell death. Bcl‐2 overexpression selectively inhibits apoptosis induced by ceramide and serum factor from AK‐5 tumor regressing animals but not actinomycin D and curcumin, whereas the pancaspase inhibitor z‐Val‐Ala‐Asp fluoromethylketone completely blocks apoptosis, irrespective of the inducer used. The ability of Bcl‐2 overexpression to block cell death does not depend on its ability to prevent cytochrome c release but correlates with its ability to prevent the dissipation of mitochondrial transmembrane potential. The results demonstrate that there are inducer dependent redundant activation pathways in a single cell, which may either be Bcl‐2 dependent or independent.