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Piceatannol suppresses the metastatic potential of MCF10A human breast epithelial cells harboring mutated H-ras by inhibiting MMP-2 expression

  • Authors:
    • Nu Ry Song
    • Mun Kyung Hwang
    • Yong-Seok Heo
    • Ki Won Lee
    • Hyong Joo Lee
  • View Affiliations / Copyright

    Affiliations: WCU Biomodulation Major, Department of Agricultural Biotechnology and Center for Food and Bioconvergence, Seoul National University, Seoul 151-921, Republic of Korea, Department of Chemistry, Konkuk University, Seoul 143-701, Republic of Korea
    Copyright: © Song et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].
  • Pages: 775-784
    |
    Published online on: July 18, 2013
       https://doi.org/10.3892/ijmm.2013.1449
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Abstract

Metastasis is one of the most threatening features of the oncogenic process and the main cause of cancer-related mortality. Several studies have demonstrated that matrix metalloproteinases (MMPs) are critical for tumor invasion and metastasis. Resveratrol (3,5,4'-trihydroxystilbene), a phenolic compound of red wine, has been reported to be a natural chemopreventive agent. However, the cancer preventive effects of piceatannol (3,5,3',4'-tetrahydroxystilbene), a metabolite of resveratrol and the underlying molecular mechanisms have not yet been fully elucidated. In this study, we report that piceatannol inhi­bits H-ras-induced MMP-2 activity and the invasive phenotype of MCF10A human breast epithelial cells harboring mutated H-ras (H-ras MCF10A cells) more effectively than resveratrol. Piceatannol attenuated the H-ras-induced phosphorylation of Akt in a time- and dose-dependent manner, whereas resveratrol, at the same concentrations, did not exert an inhibitory effect. In vitro kinase assays demonstrated that piceatannol significantly inhibited phosphatidylinositol 3-kinase (PI3K) activity and suppressed phospha­tidylinositol (3,4,5)-trisphosphate (PIP3) expression in the H-ras MCF10A cells. Ex vivo pull-down assays revealed that piceatannol directly bound to PI3K, inhibiting PI3K activity. Data from molecular docking suggested that piceatannol is a more tight-binding inhibitor than resveratrol due to the additional hydrogen bond between the hydroxyl group and the backbone amide group of Val882 in the ATP-binding pocket of PI3K.
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Copy and paste a formatted citation
Spandidos Publications style
Song NR, Hwang MK, Heo Y, Lee KW and Lee HJ: Piceatannol suppresses the metastatic potential of MCF10A human breast epithelial cells harboring mutated H-ras by inhibiting MMP-2 expression. Int J Mol Med 32: 775-784, 2013.
APA
Song, N.R., Hwang, M.K., Heo, Y., Lee, K.W., & Lee, H.J. (2013). Piceatannol suppresses the metastatic potential of MCF10A human breast epithelial cells harboring mutated H-ras by inhibiting MMP-2 expression. International Journal of Molecular Medicine, 32, 775-784. https://doi.org/10.3892/ijmm.2013.1449
MLA
Song, N. R., Hwang, M. K., Heo, Y., Lee, K. W., Lee, H. J."Piceatannol suppresses the metastatic potential of MCF10A human breast epithelial cells harboring mutated H-ras by inhibiting MMP-2 expression". International Journal of Molecular Medicine 32.4 (2013): 775-784.
Chicago
Song, N. R., Hwang, M. K., Heo, Y., Lee, K. W., Lee, H. J."Piceatannol suppresses the metastatic potential of MCF10A human breast epithelial cells harboring mutated H-ras by inhibiting MMP-2 expression". International Journal of Molecular Medicine 32, no. 4 (2013): 775-784. https://doi.org/10.3892/ijmm.2013.1449
Copy and paste a formatted citation
x
Spandidos Publications style
Song NR, Hwang MK, Heo Y, Lee KW and Lee HJ: Piceatannol suppresses the metastatic potential of MCF10A human breast epithelial cells harboring mutated H-ras by inhibiting MMP-2 expression. Int J Mol Med 32: 775-784, 2013.
APA
Song, N.R., Hwang, M.K., Heo, Y., Lee, K.W., & Lee, H.J. (2013). Piceatannol suppresses the metastatic potential of MCF10A human breast epithelial cells harboring mutated H-ras by inhibiting MMP-2 expression. International Journal of Molecular Medicine, 32, 775-784. https://doi.org/10.3892/ijmm.2013.1449
MLA
Song, N. R., Hwang, M. K., Heo, Y., Lee, K. W., Lee, H. J."Piceatannol suppresses the metastatic potential of MCF10A human breast epithelial cells harboring mutated H-ras by inhibiting MMP-2 expression". International Journal of Molecular Medicine 32.4 (2013): 775-784.
Chicago
Song, N. R., Hwang, M. K., Heo, Y., Lee, K. W., Lee, H. J."Piceatannol suppresses the metastatic potential of MCF10A human breast epithelial cells harboring mutated H-ras by inhibiting MMP-2 expression". International Journal of Molecular Medicine 32, no. 4 (2013): 775-784. https://doi.org/10.3892/ijmm.2013.1449
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