Impact of Procyanidins from Different Berries on Caspase 8 Activation in Colon Cancer

Oxid Med Cell Longev. 2015:2015:154164. doi: 10.1155/2015/154164. Epub 2015 Jun 9.

Abstract

Scope: The aim of this work is to identify which proapoptotic pathway is induced in human colon cancer cell lines, in contact with proanthocyanidins extracted from various berries.

Methods and results: Proanthocyanidins (Pcys) extracted from 11 berry species are monitored for proapoptotic activities on two related human colon cancer cell lines: SW480-TRAIL-sensitive and SW620-TRAIL-resistant. Apoptosis induction is monitored by cell surface phosphatidylserine (PS) detection. Lowbush blueberry extract triggers the strongest activity. When tested on the human monocytic cell line THP-1, blueberry Pcys are less effective for PS externalisation and DNA fragmentation is absent, highlighting a specificity of apoptosis induction in gut cells. In Pcys-treated gut cell lines, caspase 8 (apoptosis extrinsic pathway) but not caspase 9 (apoptosis intrinsic pathway) is activated after 3 hours through P38 phosphorylation (90 min), emphasizing the potency of lowbush blueberry Pcys to eradicate gut TRAIL-resistant cancer cells.

Conclusion: We highlight here that berries Pcys, especially lowbush blueberry Pcys, are of putative interest for nutritional chemoprevention of colorectal cancer in view of their apoptosis induction in a human colorectal cancer cell lines.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects*
  • Blueberry Plants / chemistry*
  • Blueberry Plants / metabolism
  • Caspase 3 / metabolism
  • Caspase 8 / metabolism*
  • Caspase 9 / metabolism
  • Cell Line
  • Colonic Neoplasms / metabolism
  • Colonic Neoplasms / pathology
  • DNA / metabolism
  • DNA Fragmentation / drug effects
  • Drug Resistance, Neoplasm
  • Fruit / chemistry
  • Fruit / metabolism
  • Humans
  • Phosphatidylserines / metabolism
  • Phosphorylation / drug effects
  • Plant Extracts / chemistry
  • Proanthocyanidins / chemistry
  • Proanthocyanidins / isolation & purification
  • Proanthocyanidins / toxicity*
  • Receptors, TNF-Related Apoptosis-Inducing Ligand / metabolism
  • TNF-Related Apoptosis-Inducing Ligand / toxicity
  • Vaccinium vitis-idaea / chemistry*
  • Vaccinium vitis-idaea / metabolism
  • fas Receptor / metabolism
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • FAS protein, human
  • Phosphatidylserines
  • Plant Extracts
  • Proanthocyanidins
  • Receptors, TNF-Related Apoptosis-Inducing Ligand
  • TNF-Related Apoptosis-Inducing Ligand
  • fas Receptor
  • DNA
  • p38 Mitogen-Activated Protein Kinases
  • Caspase 3
  • Caspase 8
  • Caspase 9