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NF-κB protects rat ARL-6 hepatocellular carcinoma cells against hydrogen peroxide-induced apoptosis
| Content Provider | Scilit |
|---|---|
| Author | Qiao, Liang Yu, Jun Dent, Paul Farrell, Geoffrey |
| Copyright Year | 2005 |
| Description | 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 (H 2O 2), 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) IkBa (Adv-mIκBα), 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 H 2O 2. 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: H 2O 2 induced more apoptosis in primary hepatocytes than ARL-6 cells, and the relative resistance of ARL-6 cells to H 2O 2-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 H 2O 2 and remained prominent at 36 h. Adv-mIκBα sensitized ARL-6 cells to H 2O 2-induced apoptosis, but cell proliferation was minimally suppressed. Conclusions: Compared with normal hepatocytes, ARL-6 cells are refractory to apoptosis after exposure to H 2O 2, and this is associated with NF-κB activation. Conversely, NF-κB inhibition sensitises ARL-6 cells to H 2O 2-induced apoptosis. Sustained NF-κB activation in these HCC cells may protect them against apoptosis produced by oxidative stress. ©2005 Landes Bioscience.link_to_subscribed_fulltex |
| Related Links | https://www.tandfonline.com/doi/pdf/10.4161/cbt.4.11.2078?needAccess=true https://www.landesbioscience.com/journals/cbt/qiao4-11.pdf |
| Ending Page | 1202 |
| Page Count | 8 |
| Starting Page | 1195 |
| ISSN | 15384047 |
| e-ISSN | 15558576 |
| DOI | 10.4161/cbt.4.11.2078 |
| Journal | Cancer Biology & Therapy |
| Issue Number | 11 |
| Volume Number | 4 |
| Language | English |
| Publisher | Informa UK Limited |
| Publisher Date | 2005-11-01 |
| Access Restriction | Open |
| Subject Keyword | Journal: Cancer Biology & Therapy Gastroenterology and Hepatology Stress Hepatocytes Refractory Arl Induced Apoptosis Κb Inhibition |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cancer Research Pharmacology Molecular Medicine Oncology |
