Dataset Information

Tumor necrosis factor-? attenuates starvation-induced apoptosis through upregulation of ferritin heavy chain in hepatocellular carcinoma cells.

ABSTRACT:

Background

Tumor microenviroment is characteristic of inflammation, ischemia and starvation of nutrient. TNF-?, which is an extraordinarily pleiotropic cytokine, could be an endogenous tumor promoter in some tumor types. The basic objective of this study was to investigate the effects of TNF-? on the cell viability and apoptosis of hepatocellular carcinoma cells under serum starvation, and to identify the molecular mechanisms involved.

Methods

For this purpose, five different concentrations of TNF-? and two different serum settings (serum-cultured and serum-deprived) were used to investigate the effects of TNF-? on the cell viability and apoptosis of Hep3B and SMMC-7721 cells.

Results

TNF-? (10 ng/ml) attenuated serum starvation-induced apoptosis of hepatocellular carcinoma cells, and autophagy conferred this process. BAY11-7082, a specific inhibitor of NF-?B, reversed the suppression of serum starvation-induced apoptosis by TNF-?. Moreover, TNF-?-induced NF-?B transactivation was suppressed by autophagy inhibitor 3-MA. In addition, TNF-? up-regulated Ferritin heavy chain (FHC) transiently by NF-?B activation and FHC levels were correlated with the TNF-?-induced protection against serum starvation-mediated apoptosis of hepatocellular carcinoma cells. Furthermore, FHC-mediated inhibition of apoptosis depended on suppressing ROS accumulation.

Conclusions

Our findings suggested that autophagy conferred the TNF-? protection against serum starvation-mediated apoptosis of hepatocellular carcinoma cells, the mechanism involved with the activation of the TNF-?/ NF-?B /FHC signaling pathway.

SUBMITTER: Kou X

PROVIDER: S-EPMC3849379 | biostudies-literature | 2013 Sep

REPOSITORIES: biostudies-literature

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Publications

Tumor necrosis factor-α attenuates starvation-induced apoptosis through upregulation of ferritin heavy chain in hepatocellular carcinoma cells.

Kou Xingrui X Jing Yingying Y Deng Weijie W Sun Kai K Han Zhipeng Z Ye Fei F Yu Guofeng G Fan Qingmin Q Gao Lu L Zhao Qiudong Q Zhao Xue X Li Rong R Wei Lixin L Wu Mengchao M

BMC cancer 20130925

<h4>Background</h4>Tumor microenviroment is characteristic of inflammation, ischemia and starvation of nutrient. TNF-α, which is an extraordinarily pleiotropic cytokine, could be an endogenous tumor promoter in some tumor types. The basic objective of this study was to investigate the effects of TNF-α on the cell viability and apoptosis of hepatocellular carcinoma cells under serum starvation, and to identify the molecular mechanisms involved.<h4>Methods</h4>For this purpose, five different conc ...[more]

PMID: 24066693

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