Carvacrol Alleviates Prostate Cancer Cell Proliferation, Migration, and Invasion through Regulation of PI3K/Akt and MAPK Signaling Pathways

Oxid Med Cell Longev. 2016:2016:1469693. doi: 10.1155/2016/1469693. Epub 2016 Oct 10.

Abstract

TRPM7 is a potential therapeutic target for treatment of prostate cancer. In this study, we investigated the effects of nonselective TRPM7 inhibitor carvacrol on cell proliferation, migration, and invasion of prostate cancer PC-3 and DU145 cells. Our results showed that carvacrol blocked TRPM7-like currents in PC-3 and DU145 cells and reduced their proliferation, migration, and invasion. Moreover, carvacrol treatment significantly decreased MMP-2, p-Akt, and p-ERK1/2 protein expression and inhibited F-actin reorganization. Furthermore, consistently, TRPM7 knockdown reduced prostate cancer cell proliferation, migration, and invasion as well. Our study suggests that carvacrol may have therapeutic potential for the treatment of prostate cancer through its inhibition of TRPM7 channels and suppression of PI3K/Akt and MAPK signaling pathways.

MeSH terms

  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects*
  • Cymenes
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Male
  • Matrix Metalloproteinase 2 / metabolism
  • Microscopy, Fluorescence
  • Mitogen-Activated Protein Kinase 1 / metabolism
  • Mitogen-Activated Protein Kinase 3 / metabolism
  • Monoterpenes / toxicity*
  • Patch-Clamp Techniques
  • Phosphatidylinositol 3-Kinases / metabolism
  • Phosphorylation / drug effects
  • Prostatic Neoplasms / metabolism
  • Prostatic Neoplasms / pathology
  • Proto-Oncogene Proteins c-akt / metabolism
  • RNA Interference
  • RNA, Small Interfering / metabolism
  • Signal Transduction / drug effects*
  • TRPM Cation Channels / antagonists & inhibitors
  • TRPM Cation Channels / genetics
  • TRPM Cation Channels / metabolism

Substances

  • Cymenes
  • Monoterpenes
  • RNA, Small Interfering
  • TRPM Cation Channels
  • carvacrol
  • Proto-Oncogene Proteins c-akt
  • Trpm7 protein, rat
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3
  • Matrix Metalloproteinase 2