Differential effects of grape seed extract against human colorectal cancer cell lines: the intricate role of death receptors and mitochondria

Cancer Lett. 2013 Jun 28;334(1):69-78. doi: 10.1016/j.canlet.2012.12.015. Epub 2012 Dec 23.


Failure of anti-cancer therapy in colorectal cancer (CRC) cells involves resistance to death mechanisms. We investigated grape seed extract (GSE) ability to target CRC cells and delineated the mechanisms involved in GSE-induced CRC cell death. GSE selectively induced apoptotic death in human CRC cells; efficacy increased as the metastatic potential of the cancer cells increased. Oxidative stress, loss of mitochondrial membrane potential, modulation of pro- and anti-apoptotic proteins, and involvement of both caspase-dependent/independent apoptotic pathways contributed to GSE-induced CRC cell death. GSE intervention may serve as a multi-targeted CRC therapeutic capable of inducing selective cancer cell death.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Antineoplastic Agents, Phytogenic / pharmacology
  • Apoptosis / drug effects
  • Caspases / metabolism
  • Cell Death / drug effects
  • Cell Line, Tumor / drug effects
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / metabolism
  • Colorectal Neoplasms / pathology
  • Drug Screening Assays, Antitumor
  • Genes, p53
  • Grape Seed Extract / pharmacology*
  • Humans
  • Membrane Potential, Mitochondrial / drug effects
  • Mitochondria / drug effects*
  • Mitochondria / metabolism
  • Oxidative Stress / drug effects
  • Receptors, TNF-Related Apoptosis-Inducing Ligand / metabolism*


  • Antineoplastic Agents, Phytogenic
  • Grape Seed Extract
  • Receptors, TNF-Related Apoptosis-Inducing Ligand
  • Caspases