Chemoprevention of Low-Molecular-Weight Citrus Pectin (LCP) in Gastrointestinal Cancer Cells

Int J Biol Sci. 2016 Apr 28;12(6):746-56. doi: 10.7150/ijbs.13988. eCollection 2016.

Abstract

Background & aims: Low-molecular-weight citrus pectin (LCP) is a complex polysaccharide that displays abundant galactosyl (i.e., sugar carbohydrate) residues. In this study, we evaluated the anti-tumor properties of LCP that lead to Bcl-xL -mediated dampening of apoptosis in gastrointestinal cancer cells.

Methods: We used AGS gastric cancer and SW-480 colorectal cancer cells to elucidate the effects of LCP on cell viability, cell cycle and apoptosis in cultured cells and tumor xenografts.

Results: Significantly decreased cell viabilities were observed in LCP treated AGS and SW-480 cells (P<0.05). Cell cycle-related protein expression, such as Cyclin B1, was also decreased in LCP treated groups as compared to the untreated group. The AGS or SW-480 cell-line tumor xenografts were significantly smaller in the LCP treated group as compared the untreated group (P<0.05). LCP treatment decreased Galectin-3 (GAL-3) expression levels, which is an important gene in cancer metastasis that results in reversion of the epithelial-mesenchymal transition (EMT), and increased suppression of Bcl-xL and Survivin to promote apoptosis. Moreover, results demonstrated synergistic tumor suppressor activity of LCP and 5-FU against gastrointestinal cancer cells both in vivo and in vitro.

Conclusions: LCP effectively inhibits the growth and metastasis of gastrointestinal cancer cells, and does so in part by down-regulating Bcl-xL and Cyclin B to promote apoptosis, and suppress EMT. Thus, LCP alone or in combination with other treatments has a high potential as a novel therapeutic strategy to improve the clinical therapy of gastrointestinal cancer.

Keywords: Low-molecular-weight citrus pectin (LCP); apoptosis; caspases; epithelial- mesenchymal transition (EMT).; gastrointestinal cancer cells.

MeSH terms

  • Apoptosis / drug effects*
  • Cell Cycle / drug effects
  • Cell Cycle Proteins / metabolism
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Epithelial-Mesenchymal Transition / drug effects
  • Galectin 3 / metabolism
  • Humans
  • Pectins / pharmacology*
  • Stomach Neoplasms / metabolism
  • bcl-X Protein / metabolism

Substances

  • Cell Cycle Proteins
  • Galectin 3
  • bcl-X Protein
  • citrus pectin
  • Pectins