Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
9905751 | European Journal of Cancer | 2005 | 13 Pages |
Abstract
IFN-γ has direct anti-proliferative effects on ovarian cancer cell lines and tumour cells isolated from ovarian cancer ascites. The aim of this study was to further elucidate the mechanisms involved. An IFN-γ-mediated cell cycle blockade was detectable in synchronised cell populations. Apoptosis, which was caspase dependent, was also induced. When caspase activity was blocked, the anti-proliferative effect of IFN-γ was only partially reduced indicating independent roles for both growth inhibition and apoptosis in its actions. We have demonstrated involvement of the intrinsic apoptotic pathway; IFN-γ treatment resulted in mitochondrial membrane depolarisation, cytochrome c release into the cytosol and activation of caspase 9. Cytochrome c release was blocked by the presence of a general caspase inhibitor, suggesting a role for caspases upstream of the mitochondria. One candidate is caspase 8, which was also activated in cells treated with IFN-γ. Levels of Bid, a pro-apoptotic molecule that can mediate mitochondrial membrane permeabilisation when cleaved by caspase 8, were also decreased and indicated a potential link between these two pathways in IFN-γ-induced apoptosis. Furthermore, together with cisplatin, IFN-γ exerted a more powerful anti-proliferative effect.
Related Topics
Life Sciences
Biochemistry, Genetics and Molecular Biology
Cancer Research
Authors
Caroline Barton, Derek Davies, Fran Balkwill, Frances Burke,