Grape seed extracts modify the outcome of oxaliplatin in colon cancer cells by interfering with cellular mechanisms of drug cytotoxicity

Letizia Porcelli, Rosa Maria Iacobazzi, Anna Elisa Quatrale, Carlo Bergamini, Nunzio Denora, Pasquale Crupi, Donato Antonacci, Anita Mangia, Giovanni Simone, Nicola Silvestris, Amalia Azzariti

Research output: Contribution to journalArticle

Abstract

Grape seed extracts are commonly utilized as dietary supplements for their antioxidant properties, even from cancer patients. However, whether these natural extracts interfere with chemotherapeutics utilized in colon cancer treatment is still poorly investigated. The cytotoxicity of extracts from Italia and Palieri cultivars either alone or in combination with oxaliplatin was evaluated in colon cancer cells. Grape seed extracts displayed anti-proliferative activity depending on the concentration utilized through apoptosis induction. In combination, they affected the activation of Erk1/2 and counteracted the intrinsic and the extrinsic pathway of apoptosis, the DNA damage and the generation of ROS induced by oxaliplatin. Noteworthy grape seed extracts strongly enhanced the uptake of oxaliplatin into all cells, by affecting the cell transport system of platinum. The addition of these natural extracts to oxaliplatin strongly reduced the cellular response to oxaliplatin and allowed a huge accumulation of platinum into cells. Here, we shed light on the chemical biology underlying the combination of grape seed extracts and oxaliplatin, demonstrating that they might be detrimental to oxaliplatin effectiveness in colon cancer therapy.

Original languageEnglish
Pages (from-to)50845-50863
Number of pages19
JournalOncotarget
Volume8
Issue number31
Publication statusPublished - Feb 7 2017

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Keywords

  • Apoptosis
  • Colon cancer cells
  • Grape seed extracts
  • Oxaliplatin
  • Transport systems

ASJC Scopus subject areas

  • Oncology

Cite this

Porcelli, L., Iacobazzi, R. M., Quatrale, A. E., Bergamini, C., Denora, N., Crupi, P., Antonacci, D., Mangia, A., Simone, G., Silvestris, N., & Azzariti, A. (2017). Grape seed extracts modify the outcome of oxaliplatin in colon cancer cells by interfering with cellular mechanisms of drug cytotoxicity. Oncotarget, 8(31), 50845-50863.