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Mechanism of Fas‐mediated cell death and its enhancement by TNF‐α in human salivary gland adenocarcinoma cell line HSG
Author(s) -
Chosa Naoyuki,
Kyakumoto Seiko,
Kito Noriko,
Kamo Masaharu,
Sato Nobuko
Publication year - 2004
Publication title -
european journal of oral sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.802
H-Index - 93
eISSN - 1600-0722
pISSN - 0909-8836
DOI - 10.1111/j.1600-0722.2004.00145.x
Subject(s) - apoptosis , programmed cell death , tumor necrosis factor alpha , caspase , poly adp ribose polymerase , microbiology and biotechnology , cell culture , uvb induced apoptosis , signal transduction , chemistry , caspase 8 , cancer research , biology , endocrinology , biochemistry , enzyme , genetics , polymerase
Fas‐mediated cell death in a human salivary gland adenocarcinoma cell line (HSG) was induced by treatment of the cells with agonistic anti‐Fas antibody (CH‐11), and this cell death was enhanced by pretreatment with tumor necrosis factor alpha (TNF‐α). The mode of cell death was apoptosis, because it was accompanied by caspase activation and the cleavage of poly(ADP‐ribose) polymerase. The TNF‐α treatment of the cells increased the expression of Fas, which was accompanied by the activation of nuclear factor κB (NFκB). These results suggest that the enhancement of the apoptosis caused by TNF‐α resulted from increased sensitivity of the HSG cells to CH‐11‐mediated apoptosis due to induction of Fas protein by TNF‐α via the activation of NFκB. In order to elucidate the apoptosis signaling pathway, we examined the effect of various caspase inhibitors on the apoptosis induced by CH‐11. Fas‐mediated apoptosis of HSG cells was slightly inhibited by the caspase‐9 inhibitor although it was mainly inhibited by that for caspase‐8. Based on this finding, we consider CH‐11‐induced apoptosis in HSG cells to be mainly mediated by the type I death signaling pathway that is caused by a caspase cascade initiated by the activation of caspase‐8 at the death‐inducing signaling complex (DISC).