Brazilin Actuates Ferroptosis in Breast Cancer Cells via p53/SLC7A11/GPX4 Signaling Pathway  

作　　者：HE Dan TAN Xiao-ning LI Lin-pei GAO Wen-hui TIAN Xue-fei ZENG Pu-hua 

机构地区：[1]Hunan Academy of Chinese Medicine,Changsha 410006,China [2]School of Integrated Chinese and Western Medicine,Hunan University of Chinese Medicine,Changsha 410208,China [3]Scientific Research Department,The Affiliated Hospital of Hunan Academy of Traditional Chinese Medicine,Changsha 410006,China [4]Oncology Department,The Affiliated Hospital of Hunan Academy of Traditional Chinese Medicine,Changsha 410006,China [5]School of Traditional Chinese Medicine,Hunan University of Chinese Medicine,Changsha 410208,China

出　　处：《Chinese Journal of Integrative Medicine》2024年第11期1001-1006,共6页中国结合医学杂志（英文版）

基　　金：Supported by National Administration of Traditional Chinese Medicine Youth Qihuang Scholars Talent Project,the 73rd Batch of Grant from China Postdoctoral Science Foundation(No.2023M731069);Traditional Chinese Medicine Administration Project of Hunan Province(No.B2023086);Health Research Project of Hunan Provincial Health Commission(No.W20243081)。

摘　　要：Objective:To investigate the mechanism of induction of ferroptosis by brazilin in breast cancer cells.Methods:Breast cancer 4T1 cells were divided into 6 groups:control,brazilin 1/2 half maximal inhibitory concentration(IC_(50)),IC_(50),2×IC_(50),erastin(10μg/mL)and capecitabine(10μg/mL)groups.The effect of brazilin on the proliferation of 4T1 cells was detected by cell counting kit-8 assay,and the treatment dose of brazilin was screened.The effect of brazilin on the mitochondrial morphology of 4T1 cells,and the mitochondrial damage was evaluated under electron microscopy.The levels of Fe+,reactive oxygen species(ROS),malondialdehyde(MDA),glutathione(GSH)and glutathione peroxidase 4(GPX4)were estimated using various detection kits.The invasion and migration abilities of 4T1 cells were detected by scratch assay and transwell assay.The expressions levels of tumor protein p53,solute carrier family 7 member 11(SLC7A11),GPX4 and acyl-CoA synthetase long-chain family member 4(ACSL4)proteins were quantified by Western blot assay.Results:Compared to the control group,the 10(1/2 IC_(50)),20(IC_(50))and 40(2×IC_(50))μg/mL brazilin,erastin,and capecitabine groups showed a significant decrease in the cell survival rate,invasion and migration abilities,GSH,SLC7A11 and GPX4 protein expression levels,and mitochondrial volume and ridge(P<0.05),and a significant increase in the mitochondria membrane density,Fe2+,ROS and MDA levels,and p53 and ACSL4 protein expression levels(P<0.05).Conclusions:Brazilin actuated ferroptosis in breast cancer cells,and the underlying mechanism is mainly associated with the p53/SLC7A11/GPX4 signaling pathway.

关 键 词：breast cancer BRAZILIN ferroptosis p53/SLC7A11/GPX4 axis Chinese medicine 

分 类 号：R737.9[医药卫生—肿瘤]