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 and eosin staining and immunoblotting assay. RESULTS: We found that lotus 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.