2. Academic Validation
  3. Eupalinolide B inhibits hepatic carcinoma by inducing ferroptosis and ROS-ER-JNK pathway

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

  • Acta Biochim Biophys Sin (Shanghai). 2022 Jul 25;54(7):974-986. doi: 10.3724/abbs.2022082.
Yonghui Zhang 1 2 3 4,  Haoyang Zhang 3 4,  Jinage Mu 3 4,  Meiyue Han 3 4,  Zhihao Cao 3 4,  Feng Dong 3 4,  Tingting Wang 3 4,  Lian Pan 3 4,  Wujing Luo 3 4,  Jiaxin Li 3 4,  Huan Liu 3 4,  Lishan Jin 3 4,  Wenxuan Ding 3 4,  Yong Wei 5,  Xuesong Deng 3 4,  Dan Liu 3 4,  Xiuzhen He 3 4,  Yi Pang 3 4,  Xiao Mu 3 4,  Zhongjun Wu 1,  Dilong Chen 2 3 4
Affiliations

Affiliations

  • 1 The First Affiliated Hospital of Chongqing Medical University, Chongqing 400042, China.
  • 2 The People's Hospital Affiliated to Chongqing Three Gorges Medical College, Chongqing 404100, China.
  • 3 Chongqing Key Laboratory of Development and Utilization of Genuine Medicinal Materials in Three Gorges Reservoir Area, Chongqing 404120, China.
  • 4 Chongqing Engineering Research Center of Antitumor Natural Drugs, Chongqing 404120, China.
  • 5 Key Laboratory of Intelligent Information Processing and Control, College of Electronic and Information Engineering, Chongqing Three Gorges University, Chongqing 404110, China.
PMID: 35866605 DOI: 10.3724/abbs.2022082
Abstract

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.

Keywords

ER stress; Eupalinolide B; HO-1; JNK; ferroptosis; hepatic carcinoma.

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