文献类型：期刊文献

英文题名：Capillarisenol C, a novel bisphenol from Artemisia capillaris, induces ER stress-mediated cytotoxic autophagy in liver cancer cells

作者：Wei, Xiaofang[1,2,3,5];Wan, Haoqiang[6,7];Shen, Wanying[1,2,3,5];Yao, Jie[1,2,3];Chen, Dongling[3,4];Xie, Qiujie[1,2,3];Li, Yangfang[1,2,3];Tang, Xudong[5];Ge, Lanlan[1,2,3,4]

第一作者：魏晓凤;Wei, Xiaofang

通信作者：Ge, LL[1];Ge, LL[2];Ge, LL[3]

机构：[1]Jinan Univ, Clin Med Coll 2, Ctr Lab Longhua Branch, Shenzhen Peoples Hosp, Shenzhen 518120, Guangdong, Peoples R China;[2]Jinan Univ, Clin Med Coll 2, Dept Infect Dis, Shenzhen Peoples Hosp, Shenzhen 518120, Guangdong, Peoples R China;[3]Southern Univ Sci & Technol, Affiliated Hosp 1, Shenzhen 518120, Guangdong, Peoples R China;[4]Jinan Univ, The Clin Med Coll 2, Dept Pathol, Longhua Branch,Shenzhen Peoples Hosp, Shenzhen 518120, Guangdong, Peoples R China;[5]Gansu Univ Chinese Med, Coll Pharm, Lanzhou 730000, Gansu, Peoples R China;[6]Shenzhen Univ, Dept Pathogen Biol, Guangdong Key Lab Reg Immun & Dis, Med Sch, Shenzhen 518120, Guangdong, Peoples R China;[7]Shenzhen Univ, Med Sch, Biosafety Level Lab 3, Shenzhen 518000, Guangdong, Peoples R China

第一机构：Jinan Univ, Clin Med Coll 2, Ctr Lab Longhua Branch, Shenzhen Peoples Hosp, Shenzhen 518120, Guangdong, Peoples R China

通信机构：[1]corresponding author), Jinan Univ, Clin Med Coll 2, Ctr Lab Longhua Branch, Shenzhen Peoples Hosp, Shenzhen 518120, Guangdong, Peoples R China;[2]corresponding author), Jinan Univ, Clin Med Coll 2, Dept Infect Dis, Shenzhen Peoples Hosp, Shenzhen 518120, Guangdong, Peoples R China;[3]corresponding author), Southern Univ Sci & Technol, Affiliated Hosp 1, Shenzhen 518120, Guangdong, Peoples R China.

年份：2026

卷号：215

外文期刊名：FOOD AND CHEMICAL TOXICOLOGY

收录：;Scopus(收录号：2-s2.0-105040602467);WOS:【SCI-EXPANDED(收录号:WOS:001785096200001)】；

基金：Funding This work was supported by grants from National Natural Science Foundation of China (81903760, 82104498) , Shenzhen Science and Technology Program (JCYJ20190806151816859, JCYJ20210324 113003007, JCYJ20220530152011025, JCYJ20240813103807011) , Basic and Applied Basic Research Foundation of Guangdong Province (2021A1515110841) .

语种：英文

外文关键词：Capillarisenol C; Artemisia capillaris; Liver cancer; Cytotoxic autophagy; Endoplasmic reticulum stress

摘要：In our previous work, we isolated a novel bisphenol named capillarisenol C (Cap C) from Artemisia capillaris. The preliminary activity screening study showed that Cap C can cause cytotoxicity to hepatocellular carcinoma cells, but its mechanism is still largely unclear. In this study, we confirmed that Cap C sharply reduced the viabilities of HepG2 and Huh7 cells in a concentration-and time-dependent manner by using CCK8 assay. We aimed to investigate the molecular mechanism underlying the cytotoxicity of Cap C in liver cancer cells. The mechanism study results showed that the apoptosis inhibitor z-vad-fmk had no significantly effects on Cap C-induced HepG2 cell death. Further mechanistic studies showed that MAP1LC3-II (LC3-II) expression, LC3 puncta and GFP-p62 puncta were increased under Cap C treatment. In addition, Cap C-induced cell death was attenuated by treatment with chloroquine (CQ) or knockdown of autophagy-related gene 7 (ATG7). Western blot analysis showed that Cap C treatment led to activation ER stress protein sensors EIF2AK3/PERK and ERN1/IRE1 as well as EIF2A/ eIF2 alpha phosphorylation which have been reported to promote cytotoxic autophagy in cancer cells. Moreover, Cap C-induced cell death was abrogated with the ER stress inhibitor 4-phenylbutyrate (4-PBA) treatment. Our results demonstrated that Cap C led to autophagic cell death in liver cancers potentially by activating ER stress-related PERK-eIF2 alpha axis and IRE1 upregulation.