Constitutive activation of NF-κB in human hepatocellular carcinoma: Evidence of a cytoprotective role
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AbstractActivation of nuclear factor-κB (NF-κB) can promote or inhibit apoptosis. Oxidative stress is an important mechanism by which certain anticancer drugs kill cancer cells, and is also one of the mechanisms that activate NF-κB. We therefore examined hepatic expression of the NF-κB monomer p65 in human hepatocellular carcinoma (HCC) tissue samples from eight patients and compared it with their respective samples of surrounding liver tissues. We also studied the effect of NF-κB inhibition in human HCC cells exposed to oxidative stress, by infecting HuH7 cells with a recombinant adenovirus carrying mutant IκBα (mIκBα). Cultured HuH7 cells were infected with mIκBα or β-galactosidase (β-Gal) for 24 hr followed by treatment with increasing concentrations of H2O2. Cytotoxicity, NF-κB translocation, NF-κB DNA binding, cell proliferation, and apoptosis were determined. The monomer p65 was overexpressed in six of eight human HCC tissues. In HuH7 cells, introduction of mIκBα potently inhibited the translocation, activation, and DNA binding of NF-κB. In control (β-Gal-infected) HuH7 cells, exposure to H2O2 produced a dose-dependent increase in apoptosis, regardless of NF-κB status. mIκBα- mediated inhibition of NF-κB activation sensitized HuH7 cells to H 2O2-induced inhibition of cell growth, and further promoted cell death. Addition of H2O2 (200-500 μM) to control or mIκBα-infected HuH7 cells enhanced caspase-3 activity and cleavage. Adenovirus-mediated transfer of mIκBα potently inhibits NF-κB activity in HuH7 cells, and this enhances oxidative stress-induced cell killing. © Mary Ann Liebert, Inc.
All Author(s) ListQiao L., Zhang H., Yu J., Francisco R., Dent P., Ebert M.P.A., Rocken C., Farrell G.
Journal nameHuman Gene Therapy
Year2006
Month3
Day1
Volume Number17
Issue Number3
PublisherMary Ann Liebert Inc.
Place of PublicationUnited States
Pages280 - 290
ISSN1043-0342
LanguagesEnglish-United Kingdom

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