title: Colon cancer cell chemosensitisation by fish oil emulsion involves apoptotic mitochondria pathway.
abstract: 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.
authors.affiliation: Unit of Nutrition, Geneva University Hospital, Rue Gabrielle-Perret-Gentil 4, 1211 Geneva 14, Switzerland.
authors.forename: Virginie
authors.initials: V
authors.lastname: Granci
authors.forename: Fang
authors.initials: F
authors.lastname: Cai
authors.forename: Elena
authors.initials: E
authors.lastname: Lecumberri
authors.forename: Aurélie
authors.initials: A
authors.lastname: Clerc
authors.forename: Yves M
authors.initials: YM
authors.lastname: Dupertuis
authors.forename: Claude
authors.initials: C
authors.lastname: Pichard
mesh_terms: D000230:Adenocarcinoma / Q000178:diet therapy / Q000188:drug therapy* / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects*; D002166:Camptothecin / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003110:Colonic Neoplasms / Q000178:diet therapy / Q000188:drug therapy* / Q000378:metabolism; D003131:Combined Modality Therapy; D019587:Dietary Supplements; D019008:Drug Resistance, Neoplasm; D004655:Emulsions; D015525:Fatty Acids, Omega-3 / Q000378:metabolism / Q000627:therapeutic use; D005395:Fish Oils / Q000378:metabolism* / Q000627:therapeutic use; D005472:Fluorouracil / Q000494:pharmacology / Q000627:therapeutic use; D018565:Food-Drug Interactions; D006801:Humans; D000077146:Irinotecan; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D009944:Organoplatinum Compounds / Q000494:pharmacology / Q000627:therapeutic use; D000077150:Oxaliplatin; D014280:Triglycerides; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; C494826:BAX protein, human; D004655:Emulsions; D015525:Fatty Acids, Omega-3; D005395:Fish Oils; D009944:Organoplatinum Compounds; D014280:Triglycerides; D051028:bcl-2-Associated X Protein; C568345:fish oil triglycerides; D000077150:Oxaliplatin; D000077146:Irinotecan; D005472:Fluorouracil; D002166:Camptothecin