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Colon cancer cell chemosensitisation by fish oil emulsion involves apoptotic mitochondria pathway.
MedLine Citation:
PMID:  22874769     Owner:  NLM     Status:  Publisher    
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.
Virginie Granci; Fang Cai; Elena Lecumberri; Aurélie Clerc; Yves M Dupertuis; Claude Pichard
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-8-8
Journal Detail:
Title:  The British journal of nutrition     Volume:  -     ISSN:  1475-2662     ISO Abbreviation:  Br. J. Nutr.     Publication Date:  2012 Aug 
Date Detail:
Created Date:  2012-8-9     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0372547     Medline TA:  Br J Nutr     Country:  -    
Other Details:
Languages:  ENG     Pagination:  1-8     Citation Subset:  -    
Unit of Nutrition, Geneva University Hospital, Rue Gabrielle-Perret-Gentil 4, 1211 Geneva 14, Switzerland.
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