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Research Paper
NF-κB Protects Rat ARL-6 Hepatocellular Carcinoma Cells Against Hydrogen Peroxide-Induced Apoptosis
Liang Qiao, Jun Yu, Paul Dent and Geoffrey Farrell
volume 4 | issue 11
november 2005Pages: 1195-1202
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Background/Aims: Refractoriness of some tumours to apoptosis has been related to over-expression of NF-κB, while NF-κB inhibition can promote apoptosis in several cell types. We compared NF-κB activation profiles between normal rat hepatocytes and ARL-6 rat hepatocellular carcinoma (HCC) cells exposed to hydrogen peroxide (H2O2), and examined whether NF-κB activation could explain the observed resistance to apoptosis of ARL-6 cells. We then infected ARL-6 cells with recombinant adenovirus containing mutant (non-degradable) I?B? (Adv-mI?B?), and examined whether this rendered ARL-6 cells more sensitive to oxidative stress-induced apoptosis. Methods: Cultured primary rat hepatocytes and ARL-6 cells were treated with graded doses of H2O2. To block NF-κB, ARL-6 cells were incubated with Adv-mIκBα for 24 h. Cytotoxicity, NF-κB activation, cell proliferation, and apoptosis were determined. Results: H2O2 induced more apoptosis in primary hepatocytes than ARL-6 cells, and the relative resistance of ARL-6 cells to H2O2-induced apoptosis was associated with more pronounced NF-κB activity. In ARL-6 cells, nuclear translocation of NF-κB took place within 2 h of administering H2O2 and remained prominent at 36 h. Adv-mI?B? sensitized ARL-6 cells to H2O2-induced apoptosis, but cell proliferation was minimally suppressed. Conclusions: Compared with normal hepatocytes, ARL-6 cells are refractory to apoptosis after exposure to H2O2, and this is associated with NF-κB activation. Conversely, NF-κB inhibition sensitises ARL-6 cells to H2O2-induced apoptosis. Sustained NF-?B activation in these HCC cells may protect them against apoptosis produced by oxidative stress.
We now provide open access to journal articles published online for one year or more. This article may be downloaded at the following link:
Download PDFIf the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.