首页|3-Epi-betulinic acid 3-O-β-D-glucopyranoside(eBAG)induces autophagy by activation of AMP-activated protein kinase in hepatocellular carcinoma
3-Epi-betulinic acid 3-O-β-D-glucopyranoside(eBAG)induces autophagy by activation of AMP-activated protein kinase in hepatocellular carcinoma
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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.
eBAGAutophagyATPAMPKHepatocellular carcinoma
Mengjie Liu、Xuqiang Liu、Kaiyue He、Yongping Jian、Yujia Li、Jinrong Guo、Jingyu Yang、Zhixiang Xu、Wenyi Kang
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School of Life Sciences,Henan University,Kaifeng 475004,China
National R & D Center for Edible Fungus Processing Technology,Henan University,Kaifeng 475004,China
Joint International Research Laboratory of Food & Medicine Resource Function,Kaifeng 475004,China
Shenzhen Research Institute of Henan University,Shenzhen 518000,China
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Henan Provincial Science and Technology Research Project国家自然科学基金国家自然科学基金
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