Colon cancer cell chemosensitisation by fish oil emulsion involves apoptotic mitochondria pathway
Virginie Granci, Fang Cai, Elena Lecumberri, Aurélie Clerc, Yves M. Dupertuis, Claude Pichard
British Journal of Nutrition
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 þ/þ ) and LS174T (Bax 2/2 ) cells were co-treated for 24 -72 h with 1 mM-5-FU, 1 mM-OX or 10 mM-IRI
... r FOE dilution corresponding to 24 mM-EPA and 20·5 mM-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 0 ,6 0 -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. * Corresponding author: Y. M. Dupertuis, fax þ 41 22 372 93 63, email email@example.com Abbreviations: 5-FU, 5-fluorouracil; DAPI, 4 0 ,6 0 -diamidino-2-phenylindole; FOE, fish oil emulsion; FOL, folinic acid; FOLFOX, folinic acid and 5-fluorouracil administration combined with oxaliplatin; FOLFIRI, folinic acid and 5-fluorouracil administration combined with irinotecan; IRI, irinotecan; OX, oxaliplatin; SOE, soyabean oil emulsion; TMRM, tetramethyl rhodamine methyl ester.