Capsosiphon fulvescens glycoprotein reduces AGS gastric cancer cell migration by downregulating transforming growth factor-β1 and integrin expression

Int J Oncol. 2013 Oct;43(4):1059-65. doi: 10.3892/ijo.2013.2055. Epub 2013 Aug 7.

Abstract

Seaweeds are commonly used as functional foods and drugs. A glycoprotein (GP) from the green alga Capsosiphon fulvescens (Cf) has been reported to have antitumor activity toward various cancer cells. We previously observed that Cf-GP induced different pathways of apoptosis in AGS human gastric cancer cells. Transforming growth factor (TGF)-β1 plays an important role in cancer cell migration. Increased TGF-β1 levels increase the expression of the small GTPases and activate the FAK/PI3K/AKT pathways, resulting in the upregulation of integrin receptor proteins, which mediate the attachment of cells to surrounding tissues, cells or extracellular matrix. Thus, the inhibition of TGF-β1 signaling would downregulate integrin expression and thereby effectively decrease cell growth and migration. In the present study, we determined the effect of Cf-GP treatment on the proliferation, migration and apoptosis of AGS human gastric cancer cells. To investigate the mechanism by which Cf-GP exerts its anticancer actions, we examined the effect of Cf-GP on the expression levels of TGF-β1, FAK, PI3K, AKT, the small GTPases and integrins in AGS cells. Our findings indicate that Cf-GP inhibits AGS cell proliferation and migration by downregulating integrin expression via the TGF-β1-activated FAK/PI3K/AKT pathways. These results suggest that Cf-GP may be an important factor in the development of functional foods and therapeutic agents.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Chlorophyta / chemistry
  • Down-Regulation
  • Extracellular Matrix / genetics
  • Extracellular Matrix / pathology
  • Gene Expression Regulation, Neoplastic / drug effects*
  • Glycoproteins / administration & dosage*
  • Glycoproteins / chemistry
  • Humans
  • Integrins / biosynthesis
  • Phosphatidylinositol 3-Kinases / biosynthesis
  • Phosphorylation
  • Proto-Oncogene Proteins c-akt
  • Signal Transduction
  • Stomach Neoplasms / drug therapy*
  • Stomach Neoplasms / genetics
  • Stomach Neoplasms / pathology
  • Transforming Growth Factor beta1 / biosynthesis*

Substances

  • Glycoproteins
  • Integrins
  • Transforming Growth Factor beta1
  • Phosphatidylinositol 3-Kinases
  • Proto-Oncogene Proteins c-akt