Surfactin suppresses TPA-induced breast cancer cell invasion through the inhibition of MMP-9 expression.

Metastasis is the main cause of cancer mortality. In this study, we investigated the effects of surfactin, a cyclic lipopeptide produced by Bacillus subtilis, on cancer metastasis in vitro and the underlying molecular mechanisms involved. Surfactin inhibited the 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced invasion, migration and colony formation of human breast carcinoma cells. Western blot analysis, gelatin zymography and reverse transcription-PCR analysis revealed that matrix metalloproteinase-9 (MMP-9) expression and activation was significantly suppressed by surfactin in a dose-dependent manner. Surfactin attenuated TPA-induced nuclear translocation and activation of nuclear factor-κB (NF-κB) and activator protein-1 (AP-1). Furthermore, surfactin strongly repressed the TPA-induced phosphorylation of Akt and extracellular signal-regulated kinase (ERK). Treatment with specific inhibitors of Akt and ERK suppressed MMP-9 expression and activation. These results suggest that the surfactin-mediated inhibition of breast cancer cell invasion and MMP-9 expression involves the suppression of the NF-κB, AP-1, phosphatidylinositol 3-kinase (PI-3K)/Akt and the ERK signaling pathways. Thus surfactin may have potential value in therapeutic strategies for the treatment of breast cancer metastasis.