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

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.

• Publication year

  2013

• Venue

  International Journal of Molecular Medicine

• Publication date

  2013-07-18

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.3892/ijmm.2013.1449PMID 23877152PMCID 3812238
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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