By reducing hexokinase 2, resveratrol induces apoptosis in HCC cells addicted to aerobic glycolysis and inhibits tumor growth in mice.

Abstract

Cancer cells exhibit an altered metabolic phenotype known as the aerobic glycolysis. The expression of HK2 changes the metabolic phenotype of cells to support cancerous growth. In the present study, we investigated the inhibitory effect of resveratrol on HK2 expression and hepatocellular carcinoma (HCC) cell glycolysis. Aerobic glycolysis was observed in four HCC cell lines compared to the normal hepatic cells. Resveratrol sensitized aerobic glycolytic HCC cells to apoptosis, and this effect was attenuated by glycolytic inhibitors. The induction of mitochondrial apoptosis was associated with the decrease of HK2 expression by resveratrol in HCC cells. In addition, resveratrol enhanced sorafenib induced cell growth inhibition in aerobic glycolytic HCC cells. Combination treatment with both reagents inhibited the growth and promoted apoptosis of HCC-bearing mice. The reduction of HK2 by resveratrol provides a new dimension to clinical HCC therapies aimed at preventing disease progression.

• Authors: Weiqi Dai, Fan Wang, Jie Lu, Yujing Xia, Lei He, Kan Chen, Jingjing Li, Sainan Li, Tong Liu, Yuanyuan Zheng, Jianrong Wang, Wenxia Lu, Yuqing Zhou, Qin Yin, Huerxidan Abudumijiti, Rongxia Chen, Rong Zhang, Li Zhou, Zheng Zhou, Rong Zhu, Jing Yang, Chengfen Wang, Huawei Zhang, Yingqun Zhou, Ling Xu, Chuanyong Guo
• Journal: Oncotarget (Oncotarget) Vol. 6 Issue 15 Pg. 13703-17 (May 30 2015) ISSN: 1949-2553 [Electronic] United States
• PMID: 25938543 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Stilbenes
• Hexokinase
• Resveratrol

Topics

• Aerobiosis
• Animals
• Apoptosis (drug effects)
• Carcinoma, Hepatocellular (drug therapy, enzymology, metabolism, pathology)
• Cell Growth Processes (drug effects)
• Cell Line, Tumor
• Glycolysis (drug effects)
• Hep G2 Cells
• Hexokinase (antagonists & inhibitors, biosynthesis, metabolism)
• Humans
• Liver Neoplasms (drug therapy, enzymology, metabolism, pathology)
• Male
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Random Allocation
• Resveratrol
• Stilbenes (pharmacology)