Lotus Leaf Extract Inhibits the Cell Migration and Metastasis of ER- Breast Cancer

Abstract

Background: Patients with estrogen receptor negative (ER-) breast cancer have poor prognosis because of their high rates of metastasis. However, there is no effective treatment and drugs for ER− breast cancer metastasis. Our purpose of this study was to evaluate the effect and mechanism of lotus leaf alcohol extract (LAE) on the cell migration and metastasis of ER- breast cancer.Methods: The anti-migratory effect and mechanism of LAE were analysed in ER- breast cancer cells including SK-BR-3, MDA-MB-231 and HCC1806. Cell viability assay, wound-healing assay, RNA-sequence analysis and immunoblotting assay were applied in examining the cytotoxicity, anti-migratory effect and its possible pathways of LAE. To further investigate the inhibitory effect of LAE on metastasis in vivo, subcutaneous xenograft nude mice model and intravenous injection nude mice model were established. Lung and liver tissues were analysed by the Hematoxylin & eosin staining and immunoblotting assay.Results: We found that lotus leaf alcohol extract (LAE), not nuciferine, inhibited cell migration significantly in SK-BR-3, MDA-MB-231 and HCC1806 breast cancer cells, and did not change viability of breast cancer cells. The anti-migratory effect of LAE was dependent on TGF-β1 signaling, while independent of Wnt signaling and autophagy influx. Intracellular H2O2 participated in the TGF-β1-related inhibition of cell migration. LAE inhibited significantly the breast cancer cells metastasis in mice models. RNA-sequence analysis showed that extracellular matrix signaling pathways are associated with LAE-suppressed cell migration.Conclusions: Our findings demonstrated that lotus leaf alcohol extract inhibits the cell migration and metastasis of ER- breast cancer via TGF-β1/Erk1/2 and TGF-β1/SMAD3 signaling, which provides a potential therapeutic strategy for ER- breast cancer.