Crude extract of Rheum palmatum L inhibits migration and invasion of LS1034 human colon cancer cells acts through the inhibition of matrix metalloproteinase-2/-9 by MAPK signaling

Environ Toxicol. 2015 Jul;30(7):852-63. doi: 10.1002/tox.21962. Epub 2014 Feb 4.

Abstract

Crude extract of Rheum palmatum L. (CERP) has been used to treat different diseases in the Chinese population for decades. In this study, we investigated the anti-metastasis effects of CERP on LS1034 human colorectal cancer cells in vitro and examined potential mechanisms of its effects. CERP significantly inhibited cell migration and invasion of LS1034 cells. We also found that CERP inhibited protein levels of matrix metalloproteinases-2 (MMP-2) and matrix metalloproteinases-9 (MMP-9), and cytosolic NF-kB p65, RHO A, ROCK 1. Furthermore, we found CERP inhibited protein levels of GRB2, SOS1, MKK7, FAK, Rho A, ROCK 1, VEGF, PKC, AKT, phosphor-AKT (Thr308), Cyclin D, iNOS, COX2, NF-kB p65, p-ERK1/2, p-JNK1/2, p-p38, p-c-jun, MMP-2, MMP-9, MMP-1, MMP-7, MMP-10, UPA and increased the protein level of Ras in LS1034 cells. In conclusion, our results suggest that CERP may be used as a novel anti-metastasis agent for the treatment of human colon cancer cells.

Keywords: crude extract of Rheum palmatum L; human colon cancer LS1034 cells; invasion; matrix metalloproteinases; migration.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Culture Techniques
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Survival / drug effects
  • Colonic Neoplasms / metabolism
  • Colonic Neoplasms / pathology
  • Humans
  • MAP Kinase Signaling System / drug effects*
  • Matrix Metalloproteinase 2 / metabolism*
  • Matrix Metalloproteinase 9 / metabolism*
  • Plant Extracts / chemistry
  • Plant Extracts / pharmacology*
  • Rheum / chemistry*
  • Rheum / metabolism
  • Transcription Factor RelA / metabolism
  • Wound Healing / drug effects
  • rho-Associated Kinases / metabolism
  • rhoA GTP-Binding Protein / metabolism

Substances

  • Plant Extracts
  • Transcription Factor RelA
  • ROCK1 protein, human
  • rho-Associated Kinases
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9
  • rhoA GTP-Binding Protein