Heterofucan from Sargassum filipendula induces apoptosis in HeLa cells

Mar Drugs. 2011;9(4):603-614. doi: 10.3390/md9040603. Epub 2011 Apr 14.

Abstract

Fucan is a term used to denominate a family of sulfated polysaccharides rich in sulfated l-fucose. Heterofucan SF-1.5v was extracted from the brown seaweed Sargassum filipendula by proteolytic digestion followed by sequential acetone precipitation. This fucan showed antiproliferative activity on Hela cells and induced apoptosis. However, SF-1.5v was not able to activate caspases. Moreover, SF-1.5v induced glycogen synthase kinase (GSK) activation, but this protein is not involved in the heterofucan SF-1.5v induced apoptosis mechanism. In addition, ERK, p38, p53, pAKT and NFκB were not affected by the presence of SF-1.5v. We determined that SF-1.5v induces apoptosis in HeLa mainly by mitochondrial release of apoptosis-inducing factor (AIF) into cytosol. In addition, SF-1.5v decreases the expression of anti-apoptotic protein Bcl-2 and increased expression of apoptogenic protein Bax. These results are significant in that they provide a mechanistic framework for further exploring the use of SF-1.5v as a novel chemotherapeutics against human cervical cancer.

Keywords: anticancer; apoptosis-inducing factor (AIF); fucoidan; sulfated polysaccharides.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects*
  • Apoptosis Inducing Factor / drug effects
  • Apoptosis Inducing Factor / metabolism
  • Cell Proliferation / drug effects
  • Cytosol / drug effects
  • Cytosol / metabolism
  • Female
  • Fucose / chemistry*
  • Gene Expression Regulation, Neoplastic / drug effects
  • HeLa Cells
  • Humans
  • Mitochondria / drug effects
  • Mitochondria / metabolism
  • Polysaccharides / isolation & purification
  • Polysaccharides / pharmacology*
  • Sargassum / chemistry*
  • Uterine Cervical Neoplasms / drug therapy
  • Uterine Cervical Neoplasms / pathology

Substances

  • AIFM1 protein, human
  • Apoptosis Inducing Factor
  • Polysaccharides
  • Fucose