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Synergistic Induction of Apoptosis in Murine Hepatoma Hepa1-6 Cells by IFN-γ and TNF-α

In this study, we examined the susceptibility of murine hepatoma Hepa1-6 cells to undergo IFN-γ- and/or TNF-α-induced apoptosis. IFN-γ or TNF-α alone had no demonstrable cytotoxic effects, whereas IFN-γ and TNF-α in combination induced apoptosis drastically in Hepa1-6 cells. During this apoptosis, a...

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Bibliographic Details
Published in:Biochemical and biophysical research communications 2000-06, Vol.272 (3), p.674-680
Main Authors: Sasagawa, Tadashi, Hlaing, Myint, Akaike, Toshihiro
Format: Article
Language:English
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Summary:In this study, we examined the susceptibility of murine hepatoma Hepa1-6 cells to undergo IFN-γ- and/or TNF-α-induced apoptosis. IFN-γ or TNF-α alone had no demonstrable cytotoxic effects, whereas IFN-γ and TNF-α in combination induced apoptosis drastically in Hepa1-6 cells. During this apoptosis, an increase in caspase-3- and -8-like protease activities and activation of caspase-3, identified by the appearance of its p17 fragment, were observed. Moreover, the cytotoxic induction and caspase-3 activation were effectively inhibited by Z-Asp-CH2-DCB (Z-Asp), a caspase inhibitor. Further, an elevation of cytochrome c in the cytosol, in a parallel to activation of caspase-3, was observed in a time-dependent manner. Concurrently, up-regulation of caspase-11 gene expression and processing of procaspase-11 were detected during this apoptosis. These results suggest that the caspase-3 activation, the release of cytochrome c from mitochondria, and increased caspase-11 gene expression involve in synergistic induction of apoptosis in Hepa1-6 cells by IFN-γ and TNF-α.
ISSN:0006-291X
1090-2104
DOI:10.1006/bbrc.2000.2835