Luteolin alleviates sorafenib-induced ferroptosis of BRL-3A cells through modulation of the Nrf2/GPX4 signaling pathway  

作　　者：Bo-Wen Zhang Di Yang Jin-Tao Li Mei-Hao Peng Jia-Qing Liao Qi Zhao Yi-Xi Yang Qiu-Xia Lu 

机构地区：[1]Engineering Research Center of Sichuan-Tibet Traditional Medicinal Plant,Chengdu University,Chengdu 610106,China [2]School of Food and Biological Engineering,Chengdu University,Chengdu 610106,China [3]School of Pharmacy,Chengdu University,Chengdu 610106,China

出　　处：《Traditional Medicine Research》2024年第10期1-9,共9页TMR传统医学研究

基　　金：supported by the open fund of State Key Laboratory of Southwestern Chinese Medicine Resources(No.SCMR202103)to Jian Li;Tibet Autonomous Region Science and Technology Plan(high-tech social development)project(No.XZ202201ZY0031G)to Yang YX;Anti-infective Agent Creation Engineering Research Centre of Sichuan Province,Sichuan Industrial Institute of Antibiotics,School of pharmacy,Chengdu University(No.AAC2023002)to Lu QX.

摘　　要：Background:Luteolin is a flavonoid chemical that exists in a variety of medicinal and edible plants and holds many biologically active properties in liver protection,anti-cancer,antioxidants,anti-inflammatory,neuroprotective,etc.According to its hepatoprotective properties,luteolin was selected to co-treat with sorafenib,one of the approved protein kinase inhibitors,to reduce sorafenib-induced normal liver cell damage.Methods:The BRL-3A cell line was treated with sorafenib to establish a liver injury model,followed by luteolin treatment.The cell viability was detected,and the mechanism of action was detected by immunofluorescence,western blotting,and real-time quantitative PCR.Results:The research findings demonstrated that luteolin could increase cystine/glutamate transporter xCT(SLC7A11)and glutathione peroxidase 4(GPX4)expression and display a chelating effect on iron,which led to increased glutathione and decreased malondialdehyde,Fe^(2+) and lipid reactive oxygen species contents in BRL-3A cells,and the sorafenib-induced mitochondrial membrane potential decrease was also inhibited.In addition,when sorafenib caused the accumulation of lipid reactive oxygen species,luteolin could help release this oxidative stress by activating nuclear factor E2-related factor 2(Nrf2)and up-regulating the expression of the associated genes heme oxygenase 1(HO-1)and quinone oxidoreductase 1(NQO1).Conclusion:Therefore,luteolin may ameliorate sorafenib-induced ferroptosis by activating the Nrf2-associated pathway without any impact on sorafenib anti-cancer activity.It can be used as an adjuvant to sorafenib to reduce liver injury in patients with hepatocellular carcinoma.

关 键 词：LUTEOLIN SORAFENIB liver injury ferroptosis Nrf2/GPX4 

分 类 号：R285.5[医药卫生—中药学]