echinacoside and Breast-Neoplasms

Echinacoside (ECH) is a natural anti-cancer compound and is of great value in cancer treatment. However, the mechanism underlying this effect on breast cancer (BC) was unclear.. To explore the mechanism of ECH treating BC by network pharmacology and experimental validation.. Several databases were searched to screen potential targets of ECH and obtain information on targets related to BC. STRING was applied to construct a Protein-protein interaction (PPI) network. DAVID was applied for Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Gene Expression Profiling Interactive Analysis (GEPIA) was searched for the relationship between the expression profile and overall survival of major targets in normal breast and BC tissues. Finally, the results of network pharmacology analysis were validated by experiments.. Seventeen targets of ECH overlapped with targets in BC. Ten hub targets were determined through PPI. By GO and KEGG analysis 15 entries and 25 pathways were obtained, in which phosphatidylinositol 3-kinase (PI3K), protein kinase B (AKT), hypoxia inducible factor-1 (HIF-1) and vascular endothelial growth factor (VEGF) played greater roles. Validation of key targets in the GEPIA database showed that PIK3R1 and PIK3CD remained consistent with the results of the study. Experiments in vitro showed ECH inhibited proliferation, induced apoptosis and reduced mRNA levels and protein expression of PI3K, AKT, hypoxia inducible factor-1α (HIF-1α) and vascular endothelial growth factor A (VEGFA) in MCF-7 cells. Furthermore, experiments in vivo revealed that ECH significantly reduced tumor growth, promoted apoptosis and decreased the related mRNA levels and protein expression, suggesting ECH works on BC by regulating PI3K/AKT/HIF-1α/VEGF signaling pathway.. In summary, ECH played an important role in anti-BC by regulating PI3K/AKT/HIF-1α/VEGF signaling pathway. Furthermore, ECH had multi-target and multi-pathway effects, which may be a promising natural compound for treating BC.

Topics: Breast Neoplasms; Cell Proliferation; Female; Humans; Hypoxia; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; RNA, Messenger; Signal Transduction; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factors

Echinacoside, a small molecule derived from the natural herbs Cistanche and Echinacea, shows effective anticancer abilities, but the mechanism remains unclear. By using colony formation, scratch, and transwell assays in MDA-MB-231 breast cancer cells, we confirmed the anti-breast cancer ability of Echinacoside in vitro. In addition, we found that Echinacoside can dose-dependently reduce phosho-LRP6, total LRP6, phosho-Dvl2, active β-catenin, and total β-catenin protein expression level in MDA-MB-231 and MDA-MB-468 cells by western blot. We also detected well-known Wnt targets genes, including LEF1, CD44, and cyclin D1 by real-time PCR and western blot, and Echinacoside significantly shows inhibition effect in these two breast cancer cell lines. Furthermore, we investigated its anti-breast cancer ability in an MDA-MB-231 xenograft model in vivo. Echinacoside treatment significantly reduced tumor growth, which was accompanied by a reduction in Wnt/β-catenin signaling. In summary, our results demonstrate that Echinacoside can effectively inhibit Wnt/β-catenin signaling, and therefore, it may be a promising therapeutic target to treat breast cancer.

Topics: Animals; Breast Neoplasms; Cell Line, Tumor; Cell Movement; Cell Proliferation; Female; Glycosides; Humans; Mice, Nude; Neoplasm Invasiveness; Wnt Signaling Pathway; Xenograft Model Antitumor Assays