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

Sun,Yi‑Sheng; Zhao,Zhao; Zhu,Han‑Ping

doi:10.3892/ol.2015.3220

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

Authors:
- Yi‑Sheng Sun
- Zhao Zhao
- Han‑Ping Zhu
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Affiliations: Department of Microbiology, Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou, Zhejiang 310051, P.R. China, Centre of Laboratory Medicine, Zhejiang Provincial People's Hospital, Hangzhou, Zhejiang 310014, P.R. China, Key Lab of Vaccine against Hemorrhagic Fever with Renal Syndrome, Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou, Zhejiang 310051, P.R. China
Published online on: May 18, 2015 https://doi.org/10.3892/ol.2015.3220
Pages: 536-542

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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.

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