In vitro and in vivo study of epigallocatechin-3-gallate-induced apoptosis in aerobic glycolytic hepatocellular carcinoma cells involving inhibition of phosphofructokinase activity

• DOI: 10.1038/srep28479
• Publication Date: 2016-06-29T06:11:56Z
• Authors: Sainan Li; Liwei Wu; Jiao Feng; Jingjing Li; Tong Liu; Rong Zhang; Shizan Xu; Keran Cheng; Yuqing Zhou; Shunfeng Zhou; Rui Kong; Kan Chen; Fan Wang; Yujing Xia; Jie Lu; Yingqun Zhou; Weiqi Dai; Chuanyong Guo
• Keywords: Anaerobic glycolysis; Intrinsic apoptosis

Abstract Glycolysis, as an altered cancer cell-intrinsic metabolism, is essential hallmark of cancer. Phosphofructokinase (PFK) a metabolic sensor in the glycolytic pathway and restricting substrate availability for this enzyme has been researched extensively target chemotherapy. In present study, we investigated that effects epigallocatechin-3-gallate (EGCG), active component green tea, on inhibiting cell growth inducing apoptosis by promoting shift away from glycolysis aerobic hepatocellular carcinoma (HCC) cells. EGCG modulated oligomeric structure PFK, potentially leading to stress associated suggesting acts directly suppressing PFK activity. A activity inhibitor enhanced effect, while allosteric activator reversed EGCG-induced HCC death. siRNA knockdown-induced was not activator. effect sorafenib inhibition both cells xenograft mouse model. The study suggests potential role adjuvant therapy, which merits further investigation at clinical level.