3-Epi-betulinic acid 3-O-β-D-glucopyranoside(eBAG)induces autophagy by activation of AMP-activated protein kinase in hepatocellular carcinoma  

作　　者：Mengjie Liu Xuqiang Liu Kaiyue He Yongping Jian Yujia Li Jinrong Guo Jingyu Yang Zhixiang Xu Wenyi Kang 

机构地区：[1]School of Life Sciences,Henan University,Kaifeng 475004,China [2]National R&D Center for Edible Fungus Processing Technology,Henan University,Kaifeng 475004,China [3]Joint International Research Laboratory of Food&Medicine Resource Function,Kaifeng 475004,China [4]Shenzhen Research Institute of Henan University,Shenzhen 518000,China

出　　处：《Food Science and Human Wellness》2024年第3期1453-1464,共12页食品科学与人类健康（英文）

基　　金：supported by Henan Provincial Science and Technology Research Project (212102310355);the National Natural Science Foundation of China (82020108024 and 32161143021)。

摘　　要：3-Epi-betulinic acid 3-O-β-D-glucopyranoside(eBAG)is a pentacyclic triterpene mainly distributed in food and medicinal plants,which exhibits various pharmacological properties.However,whether these functions are attributed to eBAG or additional components in these plants remain unknown.Herein,we report that eBAG exerted an inhibitory activity against hepatocellular carcinoma and esophageal cancer cells.EBAG induced non-apoptotic cell death in hepatocellular carcinoma cells.The eBAG-induced cell death was inhibited by knock-down of autophagy related gene(ATG)5 and ATG7,by administration of 3-methyladenine,a selective autophagy inhibitor that suppresses phosphoinositide 3-kinase(PI3K),and by chloroquine,a classic autophagy flux inhibitor.We demonstrated that eBAG induced an autophagy-mediated cell death.Application of eBAG mimicked cellular bioenergetics depletion leading to the reduction of intracellular ATP,activation of AMP-activated protein kinase(AMPK),and inhibition of mTOR.Co-treatment with compound C,an AMPK inhibitor,abrogated cell death induced by eBAG.We further validated the anti-tumor effect of eBAG in the murine xenograft model of hepatocellular carcinoma and found that eBAG treatment promoted the induction of autophagy and reduction of tumor growth in mice.As a functional food ingredient,eBAG is a potential therapeutic agent for the treatment of hepatocellular carcinoma and esophageal cancer.

关 键 词：eBAG AUTOPHAGY ATP AMPK Hepatocellular carcinoma 

分 类 号：R735.7[医药卫生—肿瘤]