Open AccessThe pro‐ or anti‐apoptotic function of NF‐κB is determined by the nature of the apoptotic stimulus
Author(s) -
Kaltschmidt Barbara,
Kaltschmidt Christian,
Hofmann Thomas G.,
Hehner Steffen P.,
Dröge Wulf,
Schmitz M. Lienhard
Publication year - 2000
Publication title -
european journal of biochemistry
Language(s) - English
Resource type - Journals
eISSN - 1432-1033
pISSN - 0014-2956
DOI - 10.1046/j.1432-1327.2000.01421.x
Subject(s) - hela , apoptosis , biology , cytotoxicity , tumor necrosis factor alpha , nf κb , microbiology and biotechnology , programmed cell death , transcription factor , cell , cancer cell , cancer research , in vitro , immunology , cancer , gene , genetics
To test whether the behaviour of transcription factor NF‐κB as a promoter or antagonist of apoptosis depends on the apoptotic stimulus, we determined the influence of NF‐κB on cell killing elicited by a variety of inducers within a given cell type. Inhibition of NF‐κB by genetic and pharmacological approaches rendered HeLa cells more susceptible to TNF‐α‐induced cell killing, but protected them almost completely from H 2 O 2 ‐ and pervanadate‐induced apoptosis. TNF‐α was unable to protect HeLa from H 2 O 2 ‐ and pervanadate‐induced apoptosis and further enhanced the cytotoxicity induced by these two adverse agents. Supernatants from HeLa cells stably overexpressing a transdominant negative form of IκB‐α selectively increased the cytotoxicity of TNF‐α for HeLa cells, suggesting that the enhanced susceptibility of these cells can be attributed to one or more secretable factors. Supershift experiments showed that the various apoptotic stimuli induced the same subset of DNA‐binding subunits. Therefore, the nature of the signals elicited by the respective death inducers determines whether NF‐κB induction leads to apoptosis or survival, suggesting that the manipulation of NF‐κB activity may provide a new approach to adjuvant therapy in cancer treatment.