NF-kappaB protects rat ARL-6 hepatocellular carcinoma cells against hydrogen peroxide-induced apoptosis. Export

@article{citeulike:1832609, abstract = {BACKGROUND/AIMS: Refractoriness of some tumours to apoptosis has been related to over-expression of NF-kappaB, while NF-kappaB inhibition can promote apoptosis in several cell types. We compared NF-kappaB activation profiles between normal rat hepatocytes and ARL-6 rat hepatocellular carcinoma (HCC) cells exposed to hydrogen peroxide (H2O2), and examined whether NF-kappaB 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-mIkappaBalpha), 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-kappaB, ARL-6 cells were incubated with Adv-mIkappaBalpha for 24 h. Cytotoxicity, NF-kappaB 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-kappaB activity. In ARL-6 cells, nuclear translocation of NF-kappaB took place within 2 h of administering H2O2 and remained prominent at 36 h. Adv-mIkappaBalpha 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-kappaB activation. Conversely, NF-kappaB inhibition sensitises ARL-6 cells to H2O2-induced apoptosis. Sustained NF-kappaB activation in these HCC cells may protect them against apoptosis produced by oxidative stress.}, address = {Storr Liver Unit, Westmead Millennium Institute, University of Sydney at Westmead Hospital, Westmead, NSW214-5, Australia.}, author = {Qiao, L. and Yu, J. and Dent, P. and Farrell, G.}, citeulike-article-id = {1832609}, citeulike-linkout-0 = {http://view.ncbi.nlm.nih.gov/pubmed/16177566}, citeulike-linkout-1 = {http://www.hubmed.org/display.cgi?uids=16177566}, issn = {1538-4047}, journal = {Cancer Biol Ther}, keywords = {apoptisis, arl}, month = {November}, number = {11}, pages = {1195--1202}, posted-at = {2007-10-28 17:28:13}, priority = {2}, title = {NF-kappaB protects rat ARL-6 hepatocellular carcinoma cells against hydrogen peroxide-induced apoptosis.}, url = {http://view.ncbi.nlm.nih.gov/pubmed/16177566}, volume = {4}, year = {2005} }

TY - JOUR ID - citeulike:1832609 L3 - citeulike-article-id:1832609 N2 - BACKGROUND/AIMS: Refractoriness of some tumours to apoptosis has been related to over-expression of NF-kappaB, while NF-kappaB inhibition can promote apoptosis in several cell types. We compared NF-kappaB activation profiles between normal rat hepatocytes and ARL-6 rat hepatocellular carcinoma (HCC) cells exposed to hydrogen peroxide (H2O2), and examined whether NF-kappaB 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-mIkappaBalpha), 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-kappaB, ARL-6 cells were incubated with Adv-mIkappaBalpha for 24 h. Cytotoxicity, NF-kappaB 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-kappaB activity. In ARL-6 cells, nuclear translocation of NF-kappaB took place within 2 h of administering H2O2 and remained prominent at 36 h. Adv-mIkappaBalpha 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-kappaB activation. Conversely, NF-kappaB inhibition sensitises ARL-6 cells to H2O2-induced apoptosis. Sustained NF-kappaB activation in these HCC cells may protect them against apoptosis produced by oxidative stress. IS - 11 JF - Cancer Biol Ther SN - 1538-4047 AD - Storr Liver Unit, Westmead Millennium Institute, University of Sydney at Westmead Hospital, Westmead, NSW214-5, Australia. EP - 1202 TI - NF-kappaB protects rat ARL-6 hepatocellular carcinoma cells against hydrogen peroxide-induced apoptosis. VL - 4 SP - 1195 KW - apoptisis KW - arl AU - Qiao, L AU - Yu, J AU - Dent, P AU - Farrell, G PY - 2005/11// UR - http://view.ncbi.nlm.nih.gov/pubmed/16177566 ER -