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Cytotoxic Effects of the Benzophenanthridine Alkaloids Isolated from Eomecon chionantha on MCF-7 Cells and Its Potential Mechanism
Authors:Peng Yang  Xi Zhou  Yang Xie
Institution:1. Hunan Provincial Key Laboratory for Synthetic Biology of Traditional Chinese Medicine, School of Pharmaceutical Sciences, Hunan University of Medicine, Huaihua, 418000 P. R. China

These authors contributed equally to this work.;2. School of Life Sciences, Central South University, Changsha, 410008 P. R. China

These authors contributed equally to this work.;3. Xiangya Hospital, Central South University, Changsha, 410008 P. R. China

Abstract:Seven benzophenanthridine alkaloids ( 1–7 ) were obtained from the 75 % EtOH extract of Eomecon chionantha, and exhibited moderate biological activity against MCF-7 cells. 8,12-dimethoxysanguinarine ( 1 , DSG) strongly decreased the cell viability of MCF-7 cell lines with an IC50 value of 7.12 μΜ. Based on RNA-sequencing measure and KEGG pathway enrichment analysis results, the significant differentially expressed genes (DEGs) were associated with Pathways in Cancer and PI3 K-AKT signaling pathways in DSG treated group. The potential molecular regulatory mechanisms underlying the effect of DSG induces necroptosis in MCF-7 cells via molecular docking, TEM analysis, and ROS measurement. Besides, DEGs of bone metastasis-related genes such as PI3 K, IGF1R, Notch, and Wnt mRNA were significantly downregulated in the DSG-treated group on MCF-7 cells. DSG might be selected as a bone metastasis proteins inhibitor of IL-1β, IL-6, IκBα, IGF1R, Notch, NF-κB, PTHrp, PI3 K, PKB/AKT, PTEN, TNF-α, and Wnt via molecular docking. DSG suppressed bone metastasis by regulating the expression levels of IL-1β, IL-6, PTH, CROSS, TP1NP, and OSTEOC on MCF-7 cells using ELISA measurement. Thus, our findings reveal that DSG could be a lead compound for suppressing tumor cells to bone metastasis in breast cancer cells.
Keywords:breast cancer  Eomecon chionantha  bone metastasis  necroptosis
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