Hispolon inhibits TPA-induced invasion by reducing MMP-9 expression through the NF-κB signaling pathway in MDA-MB-231 human breast cancer cells

Abstract

Abstract. Hispolon has been demonstrated to possess analgesic, anti-inflammatory and anticancer activities. However, whether hispolon prevents the invasion of breast carcinoma cells and the underlying mechanisms of its action remain unknown. In the present study, various assays, including a matrigel-based Transwell invasion assay and electrophoretic mobility shift assay, were used to investigate the anti-invasion effect of hispolon and explore its mechanism of action. The results revealed that hispolon inhibited the 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced migration and invasion of MDA-MB-231 human breast cancer cells at non-toxic concentrations. Hispolon also prevented the TPA-induced secretion of matrix metalloproteinase-9 (MMP-9) and reduced its expression at the transcriptional and translational levels. Furthermore, the phosphorylation of IκBα was reduced by hispolon, which resulted in the suppression of nuclear factor-κB (NF-κB), and p65 phosphorylation and nuclear translocation. An electrophoretic mobility shift assay demonstrated that NF-κB DNA-binding activity was induced by TPA and inhibited by hispolon. In addition, Bay 11-7082, which is a specific inhibitor of NF-κB, functioned in a similar manner as hispolon and blocked the secretion and expression of MMP-9. In conclusion, the results of the present study indicated that hispolon inhibited TPA-induced migration and invasion of MDA-MB-231 cells by reducing the secretion and expression of MMP-9 through the NF-κB signaling pathway.

Hispolon inhibits breast cancer cell migration by reversal of epithelial-to-mesenchymal transition via suppressing the ROS/ERK/Slug/E-cadherin pathway

“…Moreover, numerous studies have shown the antiproliferation activity of hispolon in many types of human cancers. Our previous research showed hispolon could inhibit TPA-induced migration and invasion of MDA-MB-231 cells by reducing MMP-9 secretion and expression, mainly through the NF-κB signaling pathway (49). In the present study, we confirmed that hispolon can inhibit the migration of MCF-7, breast cancer cells by a completely different mechanism.…”

Depletion of SENP1 suppresses the proliferation and invasion of triple-negative breast cancer cells

“…MMPs, the family of Zn-dependent endopeptidases, are associated with the invasive properties of metastatic cancer cells (28,29). It has been reported that MMP9 is overexpressed in breast cancer cells and is correlated with the invasion and metastasis of breast cancer (30,31). Given that SENP1 affected the cancer invasion and metastasis, we further investigated whether the expression of MMP9 could be controlled by SENP1.…”

Novel recombinant protein FlaA N/C increases tumor radiosensitivity via NF-κB signaling in murine breast cancer cells

“…NF-κB can activate a great number of genes involved in stress responses, inflammation, apoptosis and autophagy. NF-κB subunit 1 (P50) homodimers, or P50/P65 or P50/c-Rel heterodimers, bind to the NF-κB DNA-binding sites in the promoter regions of numerous stress-response genes, suggesting a complex regulation network at gene and physiological levels, controlled by NF-κB in stress response ( 41 ). Accumulated evidence indicates that the transcription factor NF-κB is critical for cellular protection against a variety of genotoxic agents, including irradiation, and that the inhibition of NF-κB may result in radiosensitization in radioresistant cancer cells ( 42 ).…”