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

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

doi:10.3724/abbs.2022082

Acta Biochimica et Biophysica Sinica (Jul 2022)

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

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

Affiliations

Zhang Yonghui: ["The First Affiliated Hospital of Chongqing Medical University, Chongqing 400042, China","The People’s Hospital Affiliated to Chongqing Three Gorges Medical College, Chongqing 404100, China","Chongqing Key Laboratory of Development and Utilization of Genuine Medicinal Materials in Three Gorges Reservoir Area, Chongqing 404120, China","Chongqing Engineering Research Center of Antitumor Natural Drugs, Chongqing 404120, China"]
Zhang Haoyang: ["Chongqing Key Laboratory of Development and Utilization of Genuine Medicinal Materials in Three Gorges Reservoir Area, Chongqing 404120, China","Chongqing Engineering Research Center of Antitumor Natural Drugs, Chongqing 404120, China"]
Mu Jinage: ["Chongqing Key Laboratory of Development and Utilization of Genuine Medicinal Materials in Three Gorges Reservoir Area, Chongqing 404120, China","Chongqing Engineering Research Center of Antitumor Natural Drugs, Chongqing 404120, China"]
Han Meiyue: ["Chongqing Key Laboratory of Development and Utilization of Genuine Medicinal Materials in Three Gorges Reservoir Area, Chongqing 404120, China","Chongqing Engineering Research Center of Antitumor Natural Drugs, Chongqing 404120, China"]
Cao Zhihao: ["Chongqing Key Laboratory of Development and Utilization of Genuine Medicinal Materials in Three Gorges Reservoir Area, Chongqing 404120, China","Chongqing Engineering Research Center of Antitumor Natural Drugs, Chongqing 404120, China"]
Dong Feng: ["Chongqing Key Laboratory of Development and Utilization of Genuine Medicinal Materials in Three Gorges Reservoir Area, Chongqing 404120, China","Chongqing Engineering Research Center of Antitumor Natural Drugs, Chongqing 404120, China"]
Wang Tingting: ["Chongqing Key Laboratory of Development and Utilization of Genuine Medicinal Materials in Three Gorges Reservoir Area, Chongqing 404120, China","Chongqing Engineering Research Center of Antitumor Natural Drugs, Chongqing 404120, China"]
Pan Lian: ["Chongqing Key Laboratory of Development and Utilization of Genuine Medicinal Materials in Three Gorges Reservoir Area, Chongqing 404120, China","Chongqing Engineering Research Center of Antitumor Natural Drugs, Chongqing 404120, China"]
Luo Wujing: ["Chongqing Key Laboratory of Development and Utilization of Genuine Medicinal Materials in Three Gorges Reservoir Area, Chongqing 404120, China","Chongqing Engineering Research Center of Antitumor Natural Drugs, Chongqing 404120, China"]
Li Jiaxin: ["Chongqing Key Laboratory of Development and Utilization of Genuine Medicinal Materials in Three Gorges Reservoir Area, Chongqing 404120, China","Chongqing Engineering Research Center of Antitumor Natural Drugs, Chongqing 404120, China"]
Liu Huan: ["Chongqing Key Laboratory of Development and Utilization of Genuine Medicinal Materials in Three Gorges Reservoir Area, Chongqing 404120, China","Chongqing Engineering Research Center of Antitumor Natural Drugs, Chongqing 404120, China"]
Jin Lishan: ["Chongqing Key Laboratory of Development and Utilization of Genuine Medicinal Materials in Three Gorges Reservoir Area, Chongqing 404120, China","Chongqing Engineering Research Center of Antitumor Natural Drugs, Chongqing 404120, China"]
Ding Wenxuan: ["Chongqing Key Laboratory of Development and Utilization of Genuine Medicinal Materials in Three Gorges Reservoir Area, Chongqing 404120, China","Chongqing Engineering Research Center of Antitumor Natural Drugs, Chongqing 404120, China"]
Wei Yong: ["Key Laboratory of Intelligent Information Processing and Control, College of Electronic and Information Engineering, Chongqing Three Gorges University, Chongqing 404110, China"]
Deng Xuesong: ["Chongqing Key Laboratory of Development and Utilization of Genuine Medicinal Materials in Three Gorges Reservoir Area, Chongqing 404120, China","Chongqing Engineering Research Center of Antitumor Natural Drugs, Chongqing 404120, China"]
Liu Dan: ["Chongqing Key Laboratory of Development and Utilization of Genuine Medicinal Materials in Three Gorges Reservoir Area, Chongqing 404120, China","Chongqing Engineering Research Center of Antitumor Natural Drugs, Chongqing 404120, China"]
He Xiuzhen: ["Chongqing Key Laboratory of Development and Utilization of Genuine Medicinal Materials in Three Gorges Reservoir Area, Chongqing 404120, China","Chongqing Engineering Research Center of Antitumor Natural Drugs, Chongqing 404120, China"]
Pang Yi: ["Chongqing Key Laboratory of Development and Utilization of Genuine Medicinal Materials in Three Gorges Reservoir Area, Chongqing 404120, China","Chongqing Engineering Research Center of Antitumor Natural Drugs, Chongqing 404120, China"]
Mu Xiao: ["Chongqing Key Laboratory of Development and Utilization of Genuine Medicinal Materials in Three Gorges Reservoir Area, Chongqing 404120, China","Chongqing Engineering Research Center of Antitumor Natural Drugs, Chongqing 404120, China"]
Wu Zhongjun: ["The First Affiliated Hospital of Chongqing Medical University, Chongqing 400042, China"]
Chen Dilong: ["The People’s Hospital Affiliated to Chongqing Three Gorges Medical College, Chongqing 404100, China","Chongqing Key Laboratory of Development and Utilization of Genuine Medicinal Materials in Three Gorges Reservoir Area, Chongqing 404120, China","Chongqing Engineering Research Center of Antitumor Natural Drugs, Chongqing 404120, China"]

DOI: https://doi.org/10.3724/abbs.2022082
Journal volume & issue: Vol. 54
pp. 974 – 986

Abstract

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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.

Published in Acta Biochimica et Biophysica Sinica

ISSN: 1672-9145 (Print); 1745-7270 (Online)
Publisher: China Science Publishing & Media Ltd.
Country of publisher: China
LCC subjects: Science: Chemistry: Organic chemistry: Biochemistry; Science: Biology (General): Genetics
Website: https://www.sciengine.com/ABBS/home

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