Cytotoxic Effects of the Benzophenanthridine Alkaloids Isolated from Eomecon chionantha on MCF-7 Cells and Its Potential Mechanism.

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.