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

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 24-72h with 1μm-5-FU, 1μm-OX or 10μm-IRI and/or FOE dilution corresponding to 24μm-EPA and 20·5μm-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 pathwa

Colon cancer therapy: new perspectives of nutritional manipulations using polyunsaturated fatty acids

Recent advances in the development of new therapeutic strategies combining conventional adjuvant radio/chemotherapy with nutritional manipulations with n-3 polyunsaturated fatty acids (PUFAs) are presented

Advancing from immunonutrition to a pharmaconutrition: a gigantic challenge

PURPOSE OF REVIEW: This review presents some difficulties encountered to develop and translate immunonutrition into clinical practice, and suggests moving forward to a pharmaconutrition approach. RECENT FINDINGS: Immunonutrition suffers from inconclusive and contradictory data due to the design of many of experiments and clinical studies conducted so far. The concept of a single immunonutrient formula applicable to various types of patients has also contributed to leave the medical world in a state of uncertainty. We propose to move forward to the concept of pharmaconutrition where a disease-dedicated nutrition therapy is developed following a rigorous step-by-step procedure. Nutrients are selected according to their pharmacological properties and after an in-depth evaluation of their biological interactions when mixed together. The optimum administration schedule (i.e. dose, route, timing and duration) of the new formulae is then determined in well conducted projective clinical trials where it is administered apart from the standard nutrition to ensure full delivery of the expected doses. SUMMARY: This review suggests moving forward to a pharmaconutrition approach where a rigorous step-by-step procedure would allow overcoming of the difficulties encountered to translate immunonutrition into clinical practice

In ovo method for evaluating the effect of nutritional therapies on tumor development, growth and vascularization

SummaryIn the state of the art evaluation of nutritional therapy on tumor development, growth and vascularization requires tedious and expensive in vivo assays in which a significant number of animals undergo invasive treatments. Therefore, new alternative methods to avoid animal suffering and sacrifice are welcome. This review presents a rapid and low-cost method of experimental radio/chemotherapy in tumor xenografted chicken chorioallantoic membrane (CAM), which may contribute to implement the 3R principle (Reduce, Refine, Replace). Advantages and limitations of the CAM as an experimental model in cancer research are discussed. Improving the CAM model by using tumor spheroid grafting and positron emission and computed tomography imaging would help to overcome the drawbacks of poor tumor grafting efficiency and restrained 2-D tumor growth measurement to the CAM surface. Such a simple, reliable, reproducible and quantitative method for obtaining dose–response analysis and estimating treatment schedule (i.e. type, route, dose and timing) would provide an alternative to the time-consuming and expensive evaluation step in animals before initiating clinical trials

n-3 polyunsaturated fatty acids and colon cancer prevention

The incidence of colon cancer in industrialised countries has increased since the early 1970s. It is estimated that more than one-third of cases are associated with factors related to a Western diet. Both the type and amount of dietary fats consumed have been implicated in colon cancer aetiology. Recent studies have demonstrated that n-3 polyunsaturated fatty acids (PUFAs), commonly found in fish oil (FO), could prevent colon cancer development. Evidences show that n-3 PUFAs act at different stages of cancer development and through several mechanisms including the modulation of arachidonic acid-derived prostaglandin synthesis, and Ras protein and protein kinase C expression and activity. As a result, n-3 PUFAs limit tumour cell proliferation, increase apoptotic potential along the crypt axis, promote cell differentiation and possibly limit angiogenesis. The modulatory actions of n-3 PUFAs on the immune system and their anti-inflammatory effects might also play a role in reducing colon carcinogenesis. There remains, nevertheless, some ambiguity over the safety of n-3 PUFAs with respect to secondary tumour formation. However, it appears that n-3 PUFAs may be of use in colon cancer prevention