Metastasis, which frequently occurs in breast cancer, is the major cause of mortality; therefore, new treatment strategies are urgently needed. Ferulic acid, isolated from Ferula foetida, a perennial herb, has shown antineoplastic activity in various types of cancers, such as colon and lung cancer, and central nervous system tumors. However, its potential role in suppressing breast cancer metastasis has not been fully understood. In the present study, we evaluated the antitumor activity of ferulic acid in breast cancer cell line-based in vitro and in vivo models. We first showed that ferulic acid treatment resulted in decreased viability, increased apoptosis and suppression of metastatic potential in breast cancer cell line MDA-MB-231. Furthermore, it was demonstrated that the antitumor activity of ferulic acid and its role in suppressing metastasis were regulated by the reversal of epithelial-mesenchymal transition (EMT). Consistent with our findings in vitro, the antitumor potential of ferulic acid was also verified in an MDA-MB-231 xenograft mouse model where significantly decreased tumor volume, weight and increased apoptosis were observed. Taken together, these results indicate that ferulic acid may be used as an effective therapeutic agent against breast cancer.

Metastasis is the main cause of death in breast cancer patients, which is due partly to the lack of effective treatment. Baicalin, a flavonoid compound isolated from the roots of Scutellaria lateriflora Georgi (Huang Qin), has recently been confirmed as an effective agent for the treatment of a variety of cancers. Yet, the effects and underlying molecular mechanisms of baicalin in regards to the metastasis of breast cancer remain unclear. In the present study, we found that baicalin had the potential to suppress the migration and invasion of highly aggressive breast cancer cells in a dose-dependent manner but had no impact on the viability of these cancer cells. Additionally, baicalin reversed the epithelial-to-mesenchymal transition (EMT) process, as evaluated by EMT markers in breast cancer cell lines with a change from a mesenchymal feature to an epithelial type. At the same time, the expression of beta-catenin mRNA and protein was dose-dependently down-regulated by baicalin in highly invasive breast cancer cell lines, and overexpression of beta-catenin by adenoviruses abolished these beneficial effects of baicalin in regards to the migration and invasion, and EMT of breast cancer cells. Furthermore, using a xenograft mouse model, baicalin markedly reduced liver and lung metastasis of breast cancer, inhibited expression of beta-catenin, and degraded the EMT molecules vimentin and Slug in the orthotopic tumor tissues. Taken together, all these results indicate that baicalin effectively suppresses the metastasis of breast cancer by reversing EMT, which may be mediated by downregulation of beta-catentin expression.

TTriple negative breast cancer (TNBC), characterized by its highly aggressive and metastatic features, is associated with poor prognosis and high mortality partly due to lack of effective treatment. Fisetin, a natural flavonoid compound, has been demonstrated to possess anti-cancer effects in various cancers. However, the effects and mechanisms of fisetin on metastasis of TNBC remain uncovered. In this study, we found that fisetin dose-dependently inhibited cell proliferation, migration and invasion in TNBC cell lines MDA-MB-231 and BT549 cells. In addition, fisetin reversed epithelial to mesenchymal transition (EMT) as evaluated by cell morphology and EMT markers in MDA-MB-231 and BT549 cells. Furthermore, fisetin suppressed phosphoinositol 3-kinase (PI3K)-Akt-GSK-3 signaling pathway but upregulated the expression of PTEN mRNA and protein in a concentration-dependent manner. Further, silence of PTEN by siRNA abolished these benefits of fisetin on proliferation and metastasis of TNBCs. In vivo, using the metastatic breast cancer xenograft model bearing MDA-MB-231 cells, we found that fisetin dramatically inhibited growth of primary breast tumor and reduced lung metastasis, meanwhile, the expression of EMT molecules and PTEN/Akt/GSK-3β in primary and metastatic tissues changed in the same way as those in vitro experiments. In conclusion, all these results indicated that fisetin could effectively suppress proliferation and metastasis of TNBC and reverse EMT process, which might be mediated by PTEN/Akt/GSK-3β signaling pathway.