Eupalinolide B inhibits hepatic carcinoma by inducing ferroptosis and ROS-ER-JNK pathway

作者全名："Zhang, Yonghui; Zhang, Haoyang; Mu, Jinage; Han, Meiyue; Cao, Zhihao; Dong, Feng; Wang, Tingting; Pan, Lian; Luo, Wujing; Li, Jiaxin; Liu, Huan; Jin, Lishan; Ding, Wenxuan; Wei, Yong; Deng, Xuesong; Liu, Dan; He, Xiuzhen; Pang, Yi; Mu, Xiao; Wu, Zhongjun; Chen, Dilong"

作者地址："[Zhang, Yonghui; Wu, Zhongjun] Chongqing Med Univ, Affiliated Hosp 1, Chongqing 400042, Peoples R China; [Zhang, Yonghui; Chen, Dilong] Chongqing Three Gorges Med Coll, Peoples Hosp, Chongqing 404100, Peoples R China; [Zhang, Yonghui; Zhang, Haoyang; Mu, Jinage; Han, Meiyue; Cao, Zhihao; Dong, Feng; Wang, Tingting; Pan, Lian; Luo, Wujing; Li, Jiaxin; Liu, Huan; Jin, Lishan; Ding, Wenxuan; Deng, Xuesong; Liu, Dan; He, Xiuzhen; Pang, Yi; Mu, Xiao; Chen, Dilong] Chongqing Key Lab Dev & Utilizat Genuine Med Mat, Chongqing 404120, Peoples R China; [Zhang, Yonghui; Zhang, Haoyang; Mu, Jinage; Han, Meiyue; Cao, Zhihao; Dong, Feng; Wang, Tingting; Pan, Lian; Luo, Wujing; Li, Jiaxin; Liu, Huan; Jin, Lishan; Ding, Wenxuan; Deng, Xuesong; Liu, Dan; He, Xiuzhen; Pang, Yi; Mu, Xiao; Chen, Dilong] Chongqing Engn Res Ctr Antitumor Nat Drugs, Chongqing 404120, Peoples R China; [Wei, Yong] Chongqing Three Gorges Univ, Coll Elect & Informat Engn, Key Lab Intelligent Informat Proc & Control, Chongqing 404110, Peoples R China"

通信作者："Wu, ZJ (通讯作者)，Chongqing Med Univ, Affiliated Hosp 1, Chongqing 400042, Peoples R China.; Chen, DL (通讯作者)，Chongqing Three Gorges Med Coll, Peoples Hosp, Chongqing 404100, Peoples R China.; Chen, DL (通讯作者)，Chongqing Key Lab Dev & Utilizat Genuine Med Mat, Chongqing 404120, Peoples R China.; Chen, DL (通讯作者)，Chongqing Engn Res Ctr Antitumor Nat Drugs, Chongqing 404120, Peoples R China."

来源：ACTA BIOCHIMICA ET BIOPHYSICA SINICA

ESI学科分类：BIOLOGY & BIOCHEMISTRY

WOS号：WOS:000856547000010

JCR分区：Q2

影响因子：3.7

年份：2022

卷号：54

期号：7

开始页：974

结束页：986

文献类型：Article

关键词：Eupalinolide B; hepatic carcinoma; ferroptosis; HO-1; ER stress; JNK

摘要："Primary hepatic carcinoma is a common malignant tumor. The classic molecular targeted drug sorafenib is costly and is only effective for some patients. Therefore, it is of great clinical significance to search for new molecular targeted drugs. Eupalinolide B (EB) from Eupatorium lindleyanum DC. is used to treat chronic tracheitis in clinical practice. However, the role of EB in hepatic carcinoma is unknown. In this study, we first measure the effect of EB on tumor growth in a xenograft model and PDX model. The cell proliferation and migration are also detected in human hepatocarcinoma cell lines (SMMC-7721 and HCCLM3). Then, we investigate cell cycle, cell apoptosis, cell necrosis, cell autophagy, and ferroptosis by flow cytometry, western blot analysis and electron microscopy. The results demonstrate that EB exerts anti-proliferative activity in hepatic carcinoma by blocking cell cycle arrest at S phase and inducing ferroptosis mediated by endoplasmic reticulum (ER) stress, as well as HO-1 activation. When HO-1 is inhibited, EB-induced cell death and ER protein expression are rescued. The migration-related mechanism consists of activation of the ROS-ER-JNK signaling pathway and is not connected to ferroptosis. In summary, we first discover that EB inhibits cell proliferation and migration in hepatic carcinoma, and thus EB is a promising anti-tumor compound that can be used for hepatic carcinoma."

基金机构："Science and Technology Research Program of Chongqing Municipal Education Commission [KJZD-K201902701, KJQN201802702]; Chongqing Natural Science Foundation of Chongqing Science and Technology Bureau [cstc2019jcyj-msxmX0607]; Natural Science Research Program of Chongqing Three Gorges Medical College [2018xzz01, 2019XZZ004]; Chongqing Key Disciplines of Traditional Chinese Medicine (Basic Theory of Traditional Chinese Medicine) Construction Project [16]; Bayu Scholars Program, Chongqing Three Gorges Medical College young and Middle-aged Top-notch Talent Project; Chongqing University Innovation Research Group [CXQT20030]; Chongqing Talents Plan Project [cstc2022ycjh-bgzxm0226]"

基金资助正文："This work was supported by the grants from the Science and Technology Research Program of Chongqing Municipal Education Commission (Nos. KJZD-K201902701 and KJQN201802702), the Chongqing Natural Science Foundation of Chongqing Science and Technology Bureau (No. cstc2019jcyj-msxmX0607), the Natural Science Research Program of Chongqing Three Gorges Medical College (Nos. 2018xzz01 and 2019XZZ004), the Chongqing Key Disciplines of Traditional Chinese Medicine (Basic Theory of Traditional Chinese Medicine) Construction Project (No. 16, 2021), the Bayu Scholars Program, Chongqing Three Gorges Medical College young and Middle-aged Top-notch Talent Project, the Chongqing University Innovation Research Group (No. CXQT20030), and the Chongqing Talents Plan Project (No. cstc2022ycjh-bgzxm0226)."