Saxatilin inhibits TNF-alpha-induced proliferation by suppressing AP-1-dependent IL-8 expression in the ovarian cancer cell line MDAH 2774

Mol Immunol. 2007 Feb;44(6):1409-16. doi: 10.1016/j.molimm.2006.05.001. Epub 2006 Jun 27.

Abstract

Tumor necrosis factor-alpha (TNF-alpha)-induced proliferation of cancer cell line MDAH 2774 was significantly suppressed by treating the cells with saxatilin, a snake venom disintegrin. The suppressed proliferation was found to be associated with the level of interleukin-8 (IL-8) expression in the cells. TNF-alpha-induced IL-8 promoter activation that is inhibited by saxatilin treatment was dependent on activating protein-1 (AP-1) instead of nuclear factor-kappa B (NF-kappaB). Coexpression of dominant negative p38 (DN-p38) suggested that p38 is involved in the IL-8 promoter activity which is regulated by saxatilin or TNF-alpha. Experimental evidence clearly indicated that saxatilin inhibits TNF-alpha-induced proliferation of the ovarian cancer cells by suppressing IL-8 expression in AP-1-dependent manner.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / therapeutic use*
  • Cell Line, Tumor
  • Cell Proliferation*
  • Disintegrins / therapeutic use*
  • Female
  • Growth Inhibitors / therapeutic use*
  • Humans
  • Interleukin-8 / antagonists & inhibitors*
  • Interleukin-8 / biosynthesis
  • Interleukin-8 / genetics
  • Ovarian Neoplasms / drug therapy*
  • Ovarian Neoplasms / immunology
  • Transcription Factor AP-1 / antagonists & inhibitors*
  • Transcription Factor AP-1 / physiology
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors*
  • Tumor Necrosis Factor-alpha / physiology

Substances

  • Antineoplastic Agents
  • CXCL8 protein, human
  • Disintegrins
  • Growth Inhibitors
  • Interleukin-8
  • Transcription Factor AP-1
  • Tumor Necrosis Factor-alpha
  • saxatilin