Chlorogenic acid induces hepatocellular carcinoma cell ferroptosis via PTGS2/AKR1C3/GPX4 axis-mediated reprogramming of arachidonic acid metabolism  

作　　者：Ling Wu Hong-Yao Chen Jing-Ting Zhang Ren-Yi Yang Zhi-Bin Wang Pei-Sen Xue Wei Peng Ke-Xiong Li Wen-Hui Gao Pu-Hua Zeng 

机构地区：[1]College of Traditional Chinese Medicine,Hunan University of Chinese Medicine,Changsha 410208,Hunan Province,China [2]Department of Oncology,Hunan Provincial Hospital of Integrated Traditional Chinese and Western Chinese,Changsha 410006,Hunan Province,China [3]Cancer Research Institute of Hunan Academy of Traditional Chinese Medicine,Hunan Provincial Hospital of Integrated Traditional Chinese and Western Chinese,Changsha 410006,Hunan Province,China

出　　处：《World Journal of Gastrointestinal Oncology》2025年第3期202-220,共19页世界胃肠肿瘤学杂志(英文)

基　　金：the National Natural Science Foundation of China,No.82074425;Natural Foundation of Hunan Province,No.2023JJ30364 and No.2023JJ30361;Hunan Provincial Key R&D Program,No.2023SK2057;Key Project of Hunan Provincial Administration of Traditional Chinese Medicine,No.A2023042.

摘　　要：BACKGROUND Ferroptosis is an iron-dependent programmed non-apoptotic cell death characterized by the accumulation of free iron ions and lipid peroxidation.It is associated with the inactivation of glutathione peroxidase(GPX)and the accumulation of lipid peroxides within cells.Ferroptosis is closely related to the occurrence and development of hepatocellular carcinoma(HCC).Chlorogenic acid(CGA),an important bioactive component found in 61 traditional Chinese medicines such as Eucommia ulmoides,has been extensively studied for its effects on various malignant tumors.However,the specific role and potential mechanism of CGA in HCC remain unclear.AIM To elucidate the anti-tumor characteristics and potential mechanisms of CGA in inducing ferroptosis in HCC cells.METHODS The effects of CGA on the proliferation,migration,and invasion of HCC cells were evaluated through in vitro experiments.Bioinformatics analysis combined with network pharmacology was used to study the potential targets and molecular mechanisms of CGA intervention in HCC ferroptosis.In vitro experiments were conducted to verify and explore the anti-HCC effects and mechanisms of CGA through the ferroptosis pathway.RESULTS In vitro experiments showed that CGA dose-dependently inhibited the proliferation,invasion,and migration of HCC cells.Bioinformatics analysis combined with network pharmacology revealed that the pathway of CGA intervention in HCC cell ferroptosis was mainly enriched in the prostaglandin endoperoxide synthase 2(PTGS2)/aldoketo reductase family 1 member C3(AKR1C3)/GPX4 signaling pathway,which was associated with arachidonic acid.In vitro experiments further confirmed that CGA-induced ferroptosis in HCC cells was related to mitochondrial damage through the reprogramming of arachidonic acid metabolism by regulating the PTGS2/AKR1C3/GPX4 signaling pathway.CONCLUSION This study demonstrates that CGA inhibits HCC cell proliferation,migration,and invasion by inducing ferroptosis through the PTGS2/AKR1C3/GPX4 axis,suggesting its potential as a no

关 键 词：Chlorogenic acid Hepatocellular carcinoma Ferroptosis Prostaglandin endoperoxide synthase 2/aldo-keto reductase family 1 member C3/glutathione peroxidase 4 axis BIOINFORMATICS In vitro experiment 

分 类 号：R73[医药卫生—肿瘤]