Colon cancer cell chemosensitisation by fish oil emulsion involves apoptotic mitochondria pathway

Br J Nutr. 2013 Apr 14;109(7):1188-95. doi: 10.1017/S000711451200308X. Epub 2012 Aug 8.


Adjuvant use of safe compounds with anti-tumour properties has been proposed to improve cancer chemotherapy outcome. We aimed to investigate the effects of fish oil emulsion (FOE) rich in n-3 PUFA with the standard chemotherapeutic agents 5-fluorouracil (5-FU), oxaliplatin (OX) or irinotecan (IRI) on two human colorectal adenocarcinoma cells with different genetic backgrounds. The HT-29 (Bax+/+) and LS174T (Bax-/-) cells were co-treated for 24-72 h with 1 μm-5-FU, 1 μm-OX or 10 μm-IRI and/or FOE dilution corresponding to 24 μm-EPA and 20·5 μm-DHA. Soyabean oil emulsion (SOE) was used as isoenergetic and isolipid control. Cell viability, apoptosis and nuclear morphological changes were evaluated by cytotoxic colorimetric assay, flow cytometry analysis with annexin V and 4',6'-diamidino-2-phenylindole staining, respectively. A cationic fluorescent probe was used to evaluate mitochondrial dysfunction, and protein expression involved in mitochondrial apoptosis was determined by Western blot. In contrast to SOE, co-treatment with FOE enhanced significantly the pro-apoptotic and cytotoxic effects of 5-FU, OX or IRI in HT-29 but not in LS174T cells (two-way ANOVA, P <0.01). These results were confirmed by the formation of apoptotic bodies in HT-29 cells. A significant increase in mitochondrial membrane depolarisation was observed after the combination of 5-FU or IRI with FOE in HT-29 but not in LS174T cells (P <0.05). Co-administration of FOE with the standard agents, 5-FU, OX and IRI, could be a good alternative to increase the efficacy of chemotherapeutic protocols through a Bax-dependent mitochondrial pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / diet therapy
  • Adenocarcinoma / drug therapy*
  • Adenocarcinoma / metabolism
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / therapeutic use
  • Apoptosis / drug effects*
  • Camptothecin / analogs & derivatives
  • Camptothecin / pharmacology
  • Camptothecin / therapeutic use
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Colonic Neoplasms / diet therapy
  • Colonic Neoplasms / drug therapy*
  • Colonic Neoplasms / metabolism
  • Combined Modality Therapy
  • Dietary Supplements
  • Drug Resistance, Neoplasm*
  • Emulsions
  • Fatty Acids, Omega-3 / metabolism
  • Fatty Acids, Omega-3 / therapeutic use
  • Fish Oils / metabolism*
  • Fish Oils / therapeutic use
  • Fluorouracil / pharmacology
  • Fluorouracil / therapeutic use
  • Food-Drug Interactions
  • Humans
  • Irinotecan
  • Membrane Potential, Mitochondrial / drug effects
  • Mitochondria / drug effects*
  • Mitochondria / metabolism
  • Organoplatinum Compounds / pharmacology
  • Organoplatinum Compounds / therapeutic use
  • Oxaliplatin
  • Triglycerides
  • bcl-2-Associated X Protein / metabolism


  • Antineoplastic Agents
  • BAX protein, human
  • Emulsions
  • Fatty Acids, Omega-3
  • Fish Oils
  • Organoplatinum Compounds
  • Triglycerides
  • bcl-2-Associated X Protein
  • fish oil triglycerides
  • Oxaliplatin
  • Irinotecan
  • Fluorouracil
  • Camptothecin