Lotus leaf extract inhibits ER- breast cancer cell migration and metastasis

Background: Patients with estrogen receptor negative (ER-) breast cancer have poor prognosis due to 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 of lotus leaf alcohol extract (LAE) on the cell migration and metastasis of ER- breast cancer. Methods: : The anti-migratory effect of LAE were analyzed in ER- breast cancer cells including SK-BR-3, MDA-MB-231 and HCC1806 cell lines. Cell viability assay, wound-healing assay, RNA-sequence analysis and immunoblotting assay were used to evaluate the cytotoxicity and anti-migratory effect of LAE. To further investigate the inhibitory effect of LAE on metastasis in vivo , subcutaneous xenograft and intravenous injection nude mice models were established. Lung and liver tissues were analyzed 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 affect 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 H 2 O 2 was involved 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, at least in part, via TGF-β1/Erk1/2 and TGF-β1/SMAD3 signaling pathways, which provides a potential therapeutic strategy for ER- breast cancer.