Arctii Fructus Inhibits Colorectal Cancer Cell Proliferation and MMPs Mediated Invasion via AMPK

Am J Chin Med. 2017;45(6):1309-1325. doi: 10.1142/S0192415X17500720. Epub 2017 Aug 22.

Abstract

Although Arctii Fructus (AF) has been shown to have various pharmacological effects, there have been no studies concerning the inhibitory effects of AF on the metastatic properties of colorectal cancer (CRC). The aim of this study was to investigate whether AF could suppress CRC progression by inhibiting cell growth, epithelial-mesenchymal transition (EMT), migration, and the invasion ability of CRC cells. AF decreased proliferation of CRC cells by inducing cell cycle arrest and apoptosis via extrinsic and intrinsic apoptotic pathways. Regarding metastatic properties, AF inhibited EMT by increasing the expression of the epithelial marker, E-cadherin, and decreasing the expression of the mesenchymal marker, N-cadherin, in CT26 cells. Moreover, AF decreased the migration and invasion of CT26 cells by inhibiting matrix metalloproteinase-2 (MMP-2) and MMP-9 activity. We confirmed that the decreased invasion ability and MMP-9 activity by AF treatment involved AMP-activated protein kinase (AMPK) activation. Collectively, this study demonstrates that AF inhibits the proliferation and metastatic properties of CRC cells.

Keywords: AMPK; Apoptosis; Arctii Fructus; Colorectal Cancer; MMP-9; Metastasis.

MeSH terms

  • AMP-Activated Protein Kinases / metabolism*
  • Animals
  • Apoptosis / drug effects
  • Arctium / chemistry*
  • Cadherins / metabolism
  • Cell Cycle Checkpoints / drug effects
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects*
  • Cell Survival
  • Colorectal Neoplasms / pathology*
  • Epithelial-Mesenchymal Transition / drug effects
  • Epithelial-Mesenchymal Transition / genetics
  • Fruit / chemistry*
  • Matrix Metalloproteinase 2 / metabolism*
  • Matrix Metalloproteinase 9 / metabolism*
  • Mice
  • Neoplasm Invasiveness / genetics
  • Neoplasm Invasiveness / pathology
  • Neoplasm Metastasis
  • Plant Extracts / isolation & purification
  • Plant Extracts / pharmacology*

Substances

  • Cadherins
  • Plant Extracts
  • AMP-Activated Protein Kinases
  • Matrix Metalloproteinase 2
  • Mmp2 protein, mouse
  • Matrix Metalloproteinase 9
  • Mmp9 protein, mouse