Tumor necrosis factor-α 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-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.

METHODS:

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

RESULTS:

TNF-α (10 ng/ml) attenuated serum starvation-induced apoptosis of hepatocellular carcinoma cells, and autophagy conferred this process. BAY11-7082, a specific inhibitor of NF-κB, reversed the suppression of serum starvation-induced apoptosis by TNF-α. Moreover, TNF-α-induced NF-κB transactivation was suppressed by autophagy inhibitor 3-MA. In addition, TNF-α up-regulated Ferritin heavy chain (FHC) transiently by NF-κB activation and FHC levels were correlated with the TNF-α-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-α protection against serum starvation-mediated apoptosis of hepatocellular carcinoma cells, the mechanism involved with the activation of the TNF-α/ NF-κB /FHC signaling pathway.

• Authors: Xingrui Kou, Yingying Jing, Weijie Deng, Kai Sun, Zhipeng Han, Fei Ye, Guofeng Yu, Qingmin Fan, Lu Gao, Qiudong Zhao, Xue Zhao, Rong Li, Lixin Wei, Mengchao Wu
• Journal: BMC cancer (BMC Cancer) Vol. 13 Pg. 438 (Sep 25 2013) ISSN: 1471-2407 [Electronic] England
• PMID: 24066693 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• NF-kappa B
• Reactive Oxygen Species
• Tumor Necrosis Factor-alpha
• 3-methyladenine
• Apoferritins
• Adenine

Topics

• Adenine (analogs & derivatives, pharmacology)
• Apoferritins (genetics)
• Apoptosis (drug effects)
• Carcinoma, Hepatocellular (genetics, metabolism)
• Cell Line, Tumor
• Enzyme Activation (drug effects)
• Gene Expression Regulation, Neoplastic
• Humans
• Liver Neoplasms (genetics, metabolism)
• NF-kappa B (antagonists & inhibitors, metabolism)
• Reactive Oxygen Species
• Signal Transduction (drug effects)
• Tumor Necrosis Factor-alpha (metabolism)