Tetramethylpyrazine inhibits migration of SKOV3 human ovarian carcinoma cells and decreases the expression of interleukin-8 via the ERK1/2, p38 and AP-1 signaling pathways

Oncol Rep. 2011 Sep;26(3):671-9. doi: 10.3892/or.2011.1334. Epub 2011 May 31.

Abstract

Interleukin-8 (IL-8) expression by melanoma cells may influence their metastatic capabilities. Tetramethylpyrazine (TMP) from Ligusticum wallichil Franch. possesses anti-inflammatory and antitumor activities. It has recently been suggested that autocrine IL-8 may play a role in tumor cell survival, invasion and migration. The role of TMP in association with IL-8 in the tumor cell migratory process remains unclear. The purpose of the present study was to determine whether TMP influences the migratory ability of a human ovarian carcinoma cell line (SKOV3) via regulation of IL-8 expression in vitro. Cell counts showed that treatment of SKOV3 with TMP (25-100 µg/ml) for 24 h did not decrease cell numbers, while an effect of TMP on the down-regulation of the expression of IL-8 was observed. In addition, migration of SKOV3 cells was suppressed after treatment with TMP (25-100 µg/ml) for 24 h. Therefore, expression of IL-8 by SKOV3 cells correlates with their metastatic potential. Western blot analysis revealed that ERK1/2 and p38 phosphorylation was blocked by TMP. Furthermore, IL-8 mRNA expression was inhibited significantly after co-incubation with PD98059 (ERK inhibitor) and SB203580 (p38 inhibitor), respectively. Notably, these changes were the results of activator protein-1 (AP-1) activity suppression rather than that of NF-κB. Our data suggest that TMP may inhibit tumor cell invasion and migration, at least in part, through its down-regulation of IL-8 expression. Our results provide evidence that anti-inflammation plays an important role in integrative cancer therapies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Cell Adhesion
  • Cell Line, Tumor
  • Cell Movement / drug effects*
  • Cell Survival
  • Coculture Techniques
  • Female
  • Genes, Reporter
  • Humans
  • Interleukin-8 / genetics*
  • Interleukin-8 / metabolism
  • Luciferases / biosynthesis
  • Luciferases / genetics
  • Mitogen-Activated Protein Kinases / metabolism*
  • Monocytes / cytology
  • Monocytes / drug effects
  • Ovarian Neoplasms / pathology*
  • Phosphorylation
  • Pyrazines / pharmacology*
  • Signal Transduction
  • Transcription Factor AP-1 / metabolism*
  • Transcription, Genetic

Substances

  • Antineoplastic Agents
  • CXCL8 protein, human
  • Interleukin-8
  • Pyrazines
  • Transcription Factor AP-1
  • Luciferases
  • Mitogen-Activated Protein Kinases
  • tetramethylpyrazine