Suppression of MMP-9 and FAK expression by pomolic acid via blocking of NF-κB/ERK/mTOR signaling pathways in growth factor-stimulated human breast cancer cells

  • Authors:
    • Ji-Hyun Park
    • Yoon Young Cho
    • Seong Woo Yoon
    • Byoungduck Park
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  • Published online on: June 29, 2016     https://doi.org/10.3892/ijo.2016.3585
  • Pages: 1230-1240
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Abstract

The expression of matrix metalloproteinase-9 (MMP-9) and the phosphorylation of focal adhesion kinase (FAK) have been implicated in the invasion, metastasis and cell motility of cancer cells. It is considered that epidermal growth factor (EGF) may increase cell motility, an event involved in cancer cell invasion and metastasis. Pomolic acid (PA), an active triterpenoid from Euscaphis japonica, is known to inhibit the proliferation of a variety of cancer cells, but the effect of PA on the invasiveness of cancer cells is largely unknown. In this study, we first determined the molecular mechanism by which PA inhibits the migratory and invasive abilities of highly metastatic MDA-MB‑231 cells. Transwell invasion, wound-healing assay and F-actin reorganization showed that PA significantly inhibits the EGF-induced invasion, migration and cell motility by reducing expression of MMP-9 and FAK phosphorylation. In particular, PA potently suppressed the phosphorylation of nuclear factor (NF)-κB, extraceullar signal-regulated kinase (ERK), phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) signaling pathway. Furthermore, PA treatment inhibited the DNA binding activity of NF-κB and activator protein (AP)-1, which is known to mediate the expression of EGFR and MMP-9. These results suggest that PA may be a potential therapeutic candidate for treatment of breast cancer metastasis.
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September 2016
Volume 49 Issue 3

Print ISSN: 1019-6439
Online ISSN:1791-2423

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APA
Park, J., Cho, Y.Y., Yoon, S.W., & Park, B. (2016). Suppression of MMP-9 and FAK expression by pomolic acid via blocking of NF-κB/ERK/mTOR signaling pathways in growth factor-stimulated human breast cancer cells. International Journal of Oncology, 49, 1230-1240. https://doi.org/10.3892/ijo.2016.3585
MLA
Park, J., Cho, Y. Y., Yoon, S. W., Park, B."Suppression of MMP-9 and FAK expression by pomolic acid via blocking of NF-κB/ERK/mTOR signaling pathways in growth factor-stimulated human breast cancer cells". International Journal of Oncology 49.3 (2016): 1230-1240.
Chicago
Park, J., Cho, Y. Y., Yoon, S. W., Park, B."Suppression of MMP-9 and FAK expression by pomolic acid via blocking of NF-κB/ERK/mTOR signaling pathways in growth factor-stimulated human breast cancer cells". International Journal of Oncology 49, no. 3 (2016): 1230-1240. https://doi.org/10.3892/ijo.2016.3585