A herbal pair of Scutellaria barbata D.Don and Scleromitrion diffusum(Willd.)R.J.Wang induced ferroptosis in ovarian cancer A2780 cells via inducing heme catabolism and ferritinophagy  

作　　者：Zhen Wang Min Liu Guang-xing Li Liu Zhang Kai-yue Ding Si-qi Li Bing-qing Gao Peng Chen Hyok-Chol Choe Lun-yue Xia Yu-tong Yang Yi Liu Xue Sui Jun-nan Ma Lin Zhang 

机构地区：[1]Institute(College)of Integrative Medicine,Dalian Medical University,Dalian 116044,Liaoning Province,China [2]Department of General Surgery,the First Affiliated Hospital of Dalian Medical University,Dalian 116000,Liaoning Province,China [3]Advanced Institute of Medical Sciences,Dalian Medical University,Dalian 116044,Liaoning Province,China [4]Department of Clinical Medicine,Sinuiju Medical University,Sinuiju,North Pyongan 999093,Democratic People’s Republic of Korea

出　　处：《Journal of Integrative Medicine》2024年第6期665-682,共18页结合医学学报（英文版）

基　　金：supported by the National Natural Science Foundation of China(No.81873195);the Applied Basic Research Program of Liaoning Province(No.2023JH2/101300103);the Liaoning Revitalization Talents Program(No.XLYC1907113);the Dalian Medical University Foundation for Teaching Reform Project of Undergraduate Innovative Talents Training(No.111807010303)。

摘　　要：Objective:Despite the combination of Scutellaria barbata D.Don and Scleromitrion diffusum(Willd.)R.J.Wang(SB-SD)being a recognized Chinese medicinal herbal pair that is commonly used in the treatment of ovarian cancer,there is a poor understanding of their pharmacological mechanisms.This study examines the antitumor properties and potential mechanisms of SB-SD on human ovarian cancer A2780 cells through a multi-omics approach,establishing a pharmacological basis for clinical utilization.Methods:A range of mass ratios and reagents were used in the hot reflux extraction of SB-SD.The inhibitory effect of the SB-SD extracts on A2780 cell proliferation was assessed using the cell-counting kit 8assay.A zebrafish tumor implantation model was used to evaluate the effects of SB-SD extracts on tumor growth and metastasis in vivo.Transcriptomics and proteomics were used to investigate alterations in biological pathways in A2780 cells after treatment with different concentrations of SB-SD extract.Cell cycle,cell apoptosis,intracellular free iron concentration,intracellular reactive oxygen species(ROS)concentration,malondialdehyde(MDA),and mitochondrial membrane potential were measured.Real-time quantitative reverse transcription polymerase chain reaction and Western blotting were utilized to investigate the effects of heme catabolism and ferritinophagy on ferroptosis induced by SB-SD extract in A2780 cells.Results:The 70%ethanol extract of SB-SD(a mass ratio of 4:1)inhibited A2780 cell proliferation significantly with a half maximal inhibitory concentration of 660μg/m L in a concentration-and timedependent manner.Moreover,it effectively suppressed tumor growth and metastasis in a zebrafish tumor implantation model.SB-SD extract induced the accumulation of free iron,ROS,MDA,and mitochondrial damage in A2780 cells.The mechanisms might involve the upregulated expression of ferritinophagyrelated genes microtubule-associated protein 1 light chain 3,autophagy-related gene 5,and nuclear receptor coactivator 4.Conclusion:SB-SD extr

关 键 词：Scutellaria barbata D.Don Scleromitrion diffusum(Willd.)R.J.Wang Ovarian cancer Transcriptomic Proteomic Ferroptosis Heme catabolism Ferritinophagy 

分 类 号：R285[医药卫生—中药学]