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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

引用

Journal of Integrative Medicine 2024年第6期22卷 665-682页

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 Institute (College) of Integrative Medicine Dalian Medical University Department of General Surgery the First Affiliated Hospital of Dalian Medical University Advanced Institute of Medical Sciences Dalian Medical University Department of Clinical Medicine Sinuiju Medical University

Objective: Despite the combination of Scutellaria barbata D. Don and Scleromitrion diffusum(Willd.) ***(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 ***: 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 ***: 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 660 μg/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, auto

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

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