Diet, cancer, and the lipidome.

International audienceThe potential for dietary fat to interfere with the development of breast cancer by delaying its occurrence makes the identification of defined molecules a mandatory step in cancer prevention. In order to circumvent the limitations and/or bias of dietary exposure assessment tools, biomarkers of past lipid intake such as the fatty acid composition of white adipose tissue have been used. When considered separately, candidate fatty acids identified as favorable on the basis of their association with breast cancer risk have usually led to inconsistent results in animal intervention studies. This inconsistency indicates that any approach based on a single fatty acid should be abandoned for an integrated view over the complex lipid interactions which finally determines the lipidome, the lipid profile that is found in individuals. This article presents a reappraisal of the role of the lipid profile through a comprehensive reanalysis of adipose tissue fatty acid composition obtained in patients with benign or malignant breast tumors as well as in experimental animals during dietary interventions. Rather than a single fatty acid, a composite indicator combining elevated monounsaturates and low omega6/omega3 fatty acid ratio was associated with breast cancer protection. This lipidome may become the template for identifying breast cancer risk related to diet, and for designing proper dietary modifications to delay the occurrence of breast cancer, although the universality of the findings cannot be assessed from a single study

Dietary long-chain omega-3 fatty acids of marine origin: a comparison of their protective effects on coronary heart disease and breast cancers.

The relationship between high fish consumption and low mortality following coronary heart disease (CHD) and low incidence of breast cancer was first mentioned 3 decades ago. The fishes of interest are rich in omega-3 long-chain polyunsaturated fatty acids (omega-3 LC-PUFAs), especially eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), which could be the active nutrients. The current consensus about cardioprotection is that omega-3 LC-PUFAs would mainly exert antiarrhythmic effects. One of the proposed mechanisms is that circulating non-esterified LC-PUFAs partition into cardiac cells membrane phospholipids and exert a direct effect on ionic channels and/or modify intracellular calcium homeostasis. In another hypothesis, changes in the metabolism of phosphoinositides would be involved and lead to the differential activation of PKC isoforms. As compared to the mechanisms proposed for the cardioprotective effects of omega-3 LC-PUFAs, less is known about the molecular mechanisms involved in breast cancers prevention. Some proposed mechanisms such as the modulation of phosphoinositides metabolism and/or modulation of intracellular calcium homeostasis, are common to both pathologies. Other hypotheses involve the alteration of the cellular redox status induced by highly peroxidizable polyunsaturated fatty acids (FA), or the modulation of gene expression, both phenomena being tightly linked to apoptosis. In this review, we report and compare some proposed mechanisms for the involvement of omega-3 LC-PUFAs in both cardiac and breast cancer protection. Deliberately, we chose to discuss only the mechanisms, which are less described in other reviews such as ionic channels in cancer, calcium homeostasis, PKC activation or matrix metalloproteinases in both cancer and cardiac models. The leitmotiv along this review is that cardio- and cancero-protective effects use common pathways. Comparison of the cellular effects might therefore help to highlight the "protective" pathways

Voltage-gated sodium channels potentiate the invasive capacities of human non-small-cell lung cancer cell lines.

Ionic channel activity is involved in fundamental cellular behaviour and participates in cancerous features such as proliferation, migration and invasion which in turn contribute to the metastatic process. In this study, we investigated the expression and role of voltage-gated sodium channels in non-small-cell lung cancer cell lines. Functional voltage-gated sodium channels expression was investigated in normal and non-small-cell lung cancer cell lines. The measurement, in patch-clamp conditions, of tetrodotoxin-inhibitable sodium currents indicated that the strongly metastatic cancerous cell lines H23, H460 and Calu-1 possess functional sodium channels while normal and weakly metastatic cell lines do not. While all the cell lines expressed mRNA for numerous sodium channel isoforms, only H23, H460 and Calu-1 cells had a 250 kDa protein corresponding to the functional channel. The other cell lines also had another protein of 230 kDa which is not addressed to the membrane and might act as a dominant negative isoform to prevent channel activation. At the membrane potential of these cells, channels are partially open. This leads to a continuous entry of sodium, disrupting sodium homeostasis and down-stream signaling pathways. Inhibition of the channels by tetrodotoxin was responsible for a 40-50% reduction of in vitro invasion. These experiments suggest that the functional expression of voltage-gated sodium channels might be an integral component of the metastatic process in non-small-cell lung cancer cells probably through its involvement in the regulation of intracellular sodium homeostasis. These channels could serve both as novel markers of the metastatic phenotype and as potential new therapeutic targets

Alimentation et sensibilité des tumeurs aux traitements anti-cancéreux (influence des acides gras poly-insaturés N-3)

Several studies have shown that n-3 polyunsaturated fatty acids (PUFA) increase th eefficacy of anthracyclines. The general purpose of this thesis work was to understand th einteraction between n-3 PUFA and tumor sensitivity to treatment, using an autochthonous rat mammary tumor model. Our study showed that : alpha-tocopherol interferes with the n-3 PUFA induced chemosensitization of mammary tumors to epirubicin ; docosahexaenoic acid (DHA) sensitizes mammary tumors to radiation therapy (effect abolished by an alphatocopherol supply, suggesting that lipoperoxidation may be implied) ; the pivotal role of vascularization in tumor response to antitumoral drugs ; The DHA-induced enhancement of tumor response to epirubicin was accompanied by a decrease in tumor vascularization. Moreover, this chemosensitization was inhibited by alpha-tocopherol supply in a dose dependant manner.Ce travail de thèse avait pour objectif général, par une approche expérimentale de carcinogenèse mammaire chez le rat, d'observer et de comprendre la relation entre AGPI n-3 et sensibilité des tumeurs à l'action d'agents antitumoraux. Nous avons ainsi mis en évidence : une inhibition de l'effet chimiosensibilisant du DHA lors d'un apport en alphatocophérol ; l'effet sensibilisant du DHA à la radiothérapie (effet inhibé par un apport d'alpha-tocophérol, suggérant une implication de la lipopéroxydation dans ce processus) ; le lien étroit entre vascularisation tumorale, radiothérapie ou chimiothérapie, et réponse tumorale à ces traitement ; la sensibilisation par le DHA de tumeurs mammaires à l'action de l'épirubicine (effet inhibé de manière dose-dépendante par un apport d'alphatocophérol). De plus l'effet chimiosensibilisant du DHA était accompagné d'une diminution de la vascularisation, apparaissant avant même le début de la chimiothérapie.TOURS-BU Sciences Pharmacie (372612104) / SudocPARIS-BIUP (751062107) / SudocSudocFranceF

Sensibilisation de métastases de cancers du sein à la chimiothérapie de type FEC par une intervention nutritionnelle par l'acide docosahexaènoïque (DHA) (résultats d'un essai clinique de phase II)

TOURS-BU Médecine (372612103) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

4.14. Alimentation et cancer

Alimentation et cancer : relations étroites et enjeux différents L’alimentation est un des plus importants facteurs environnementaux modificateurs du risque de cancer et pourrait rendre compte de 25 à 40 % des causes de cancer accessibles à la prévention. La cancérogenèse est un processus à étapes multiples provenant à l’origine d’altérations cellulaires. Celles-ci résultent de l’accumulation d’altérations acquises de gènes qui contrôlent les processus clés de la transformatio..