Piperine depresses the migration progression via downregulating the Akt/mTOR/MMP‑9 signaling pathway in DU145 cells

Mol Med Rep. 2018 May;17(5):6363-6370. doi: 10.3892/mmr.2018.8653. Epub 2018 Feb 28.

Abstract

Piperine, an alkaloid derived from natural products, has been demonstrated to exert antitumor activities in vivo and in vitro. However, its anti‑tumor effect has not yet been illustrated in the prostate cancer (PCa) metastatic process. Thus, the present study explored the influence of piperine on PCa and the underlying molecular mechanism. Cell migration was detected via the Transwell chamber model. Total protein was identified by western blot analysis. The data revealed that piperine markedly repressed cell proliferation and migration, and induced apoptosis in PCa DU145. In addition, LY294002, an protein kinase B (Akt) inhibitor, greatly suppressed the expression level of phospho (p)‑Akt, matrix metalloproteinase (MMP)‑9 and p‑mammalian target of rapamycin (mTOR), suggesting that the activation of the Akt/mTOR/MMP‑9 signaling pathway may participate in regulating cell migration in PCa. Furthermore, piperine reduced the expression of p‑Akt, MMP‑9 and p‑mTOR. Together, these data indicated that piperine may serve as a promising novel therapeutic agent to better overcome PCa metastasis.

Keywords: piperine; matrix metalloproteinase 9; DU145; protein kinase B/mammalian target of rapamycin; migration.

MeSH terms

  • Alkaloids / pharmacology*
  • Apoptosis / drug effects
  • Benzodioxoles / pharmacology*
  • Cell Line, Tumor
  • Cell Movement / drug effects*
  • Chromones / pharmacology
  • Humans
  • Male
  • Matrix Metalloproteinase 9 / metabolism*
  • Morpholines / pharmacology
  • Neoplasm Metastasis
  • Piperidines / pharmacology*
  • Polyunsaturated Alkamides / pharmacology*
  • Prostatic Neoplasms / metabolism*
  • Prostatic Neoplasms / pathology
  • Proto-Oncogene Proteins c-akt / antagonists & inhibitors
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Signal Transduction / drug effects*
  • TOR Serine-Threonine Kinases / metabolism*

Substances

  • Alkaloids
  • Benzodioxoles
  • Chromones
  • Morpholines
  • Piperidines
  • Polyunsaturated Alkamides
  • 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
  • MTOR protein, human
  • Proto-Oncogene Proteins c-akt
  • TOR Serine-Threonine Kinases
  • MMP9 protein, human
  • Matrix Metalloproteinase 9
  • piperine