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

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外文标题：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

外文摘要：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 exam-ines 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 inhibi-tory effect of the SB-SD extracts on A2780 cell proliferation was assessed using the cell-counting kit 8 assay.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 bio-logical 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)concentra-tion,malondialdehyde(MDA),and mitochondrial membrane potential were measured.Real-time quanti-tative 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 signifi-cantly with a half maximal inhibitory concentration of 660 μg/mL in a concentration-and time-dependent 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 ferritinophagy-related genes microtubule-associated protein 1 light chain 3,autophagy-related gene 5,and nuclear receptor coactivator 4.Conclusion:SB-SD extract effectively inhibited the development of ovarian cancer both in vitro and in vivo.Its mechanism of action involved inducing ferroptosis by facilitating heme catabolism and ferritinophagy.This herbal pair holds promise as a potential therapeutic option for ovarian cancer treatment and may be utilized in combination with routine treatment to improve the treatment outcomes of ovarian cancer patients.

外文关键词：

Scutellaria barbata D.DonScleromitrion diffusum(Willd.)R.J.WangOvarian cancerTranscriptomicProteomicFerroptosisHeme catabolismFerritinophagy

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

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作者单位：

Institute(College)of Integrative Medicine,Dalian Medical University,Dalian 116044,Liaoning Province,China

Department of General Surgery,the First Affiliated Hospital of Dalian Medical University,Dalian 116000,Liaoning Province,China

Advanced Institute of Medical Sciences,Dalian Medical University,Dalian 116044,Liaoning Province,China

Department of Clinical Medicine,Sinuiju Medical University,Sinuiju,North Pyongan 999093,Democratic People's Republic of Korea

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关键词：

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

出版年：

2024

DOI：

10.1016/j.joim.2024.10.001

结合医学学报(英文版)

上海市中西医结合学会,上海长海医院

结合医学学报(英文版)

CSTPCD

影响因子：0.711

ISSN：2095-4964

年,卷(期)：2024.22(6)