A high-fat diet containing whole walnuts (Juglans regia) reduces tumour size and growth along with plasma insulin-like growth factor 1 in the transgenic adenocarcinoma of the mouse prostate model.

Prostate cancer (PCa) has been linked to fat intake, but the effects of both different dietary fat levels and types remain inconsistent and incompletely characterised. The effects on PCa in the transgenic adenocarcinoma of the mouse prostate (TRAMP) cancer model of an elevated fat (20 % of energy as fat) diet containing 155 g of whole walnuts were compared to those of an elevated fat (20 % of energy as soyabean oil) diet with matched macronutrients, tocopherols as well as a low-fat (8 % of energy as soyabean oil) diet. Mice, starting at 8 weeks of age, consumed one of the three different diets ad libitum; and prostates, livers and blood were obtained after 9, 18 or 24 weeks of feeding. No differences were observed in whole animal growth rates in either high-fat (HF) diet group, but prostate tumour weight and growth rate were reduced in the walnut diet group. Walnut diet group prostate weight, plasma insulin-like growth factor 1, resistin and LDL were lower at 18 weeks, while no statistically significant prostate weight differences by diet were seen at 9 or 24 weeks. Multiple metabolites in the livers differed by diet at 9 and 18 weeks. The walnut diet's beneficial effects probably represent the effects of whole walnuts' multiple constituents and not via a specific fatty acid or tocopherols. Moreover, as the two HF diets had dissimilar effects on prostate tumour growth rate and size, and yet had the same total fat and tocopherol composition and content, this suggests that these are not strongly linked to PCa growth

Noncariogenic Sweeteners: Sugar Substitutes for Caries Control

The evidence is clear that the incidence of dental caries is related to the frequency of eating sugar. The use of sugar substitutes is a suggested way of reducing sugar intake. A variety of noncariogenic sweeteners exists, but most have no practical value for caries control because of their technical or safety problems, taste, or cost. Urinary bladder tumorigenic effects have been reported in experimental animals treated with saccharin and cyclamates. Because of concerns for human safety, cyclamates were banned in the U.S., and saccharin use was permitted only by special legislation. The polyalcohols sorbitol and xylitol are important sugar substitutes since they are not efficient substrates for plaque bacteria and therefore produce only minimal plaque pH drop. Aspartame, with its sugar-like taste, is an excellent low-calorie sweetener now used in over 100 products under the name NutraSweet. Consumption of aspartame by normal humans is safe and does not promote tooth decay. Individuals with a need to control their phenylalanine intake should handle aspartame like any other source of phenylalanine

Loss of BCAA Catabolism during Carcinogenesis Enhances mTORC1 Activity and Promotes Tumor Development and Progression

Tumors display profound changes in cellular metabolism, yet how these changes aid the development and growth of tumors is not fully understood. Here we use a multi-omic approach to examine liver carcinogenesis and regeneration, and find that progressive loss of branched-chain amino acid (BCAA) catabolism promotes tumor development and growth. In human hepatocellular carcinomas and animal models of liver cancer, suppression of BCAA catabolic enzyme expression led to BCAA accumulation in tumors, though this was not observed in regenerating liver tissues. The degree of enzyme suppression strongly correlated with tumor aggressiveness, and was an independent predictor of clinical outcome. Moreover, modulating BCAA accumulation regulated cancer cell proliferation in vitro, and tumor burden and overall survival in vivo. Dietary BCAA intake in humans also correlated with cancer mortality risk. In summary, loss of BCAA catabolism in tumors confers functional advantages, which could be exploited by therapeutic interventions in certain cancers

Prostate tumor growth is impaired by CtBP1 depletion in high-fat diet-fed mice

Clinical and epidemiologic data suggest that obesity is associated with more aggressive forms of prostate cancer, poor prognosis, and increased mortality. C-terminal-binding protein 1 (CtBP1) is a transcription repressor of tumor suppressor genes and is activated by NADH binding. High calorie intake decreases intracellular NAD(+)/NADH ratio. The aim of this work was to assess the effect of high-fat diet (HFD) and CtBP1 expression modulation over prostate xenograft growth. We developed a metabolic syndrome-like disease in vivo model by feeding male nude mice with HFD during 16 weeks. Control diet (CD)-fed animals were maintained at the same conditions. Mice were inoculated with PC3 cells stable transfected with shCtBP1 or control plasmids. Genome-wide expression profiles and Gene Set Enrichment Analysis (GSEA) were performed from PC3.shCtBP1 versus PC3.pGIPZ HFD-fed mice tumors.Fil: Moiola, Cristian Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaFil: de Luca, Paola. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Química Biológica; ArgentinaFil: Zalazar, Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; ArgentinaFil: Cotignola, Javier Hernan. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Rodríguez Seguí, Santiago Andrés. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Fisiología, Biología Molecular y Celular; ArgentinaFil: Gardner, Kevin. National Institutes of Health; Estados UnidosFil: Meissl, Roberto Jose. Academia Nacional de Medicina de Buenos Aires; ArgentinaFil: Vallecorsa, Pablo Daniel. Academia Nacional de Medicina de Buenos Aires; ArgentinaFil: Pignataro, Omar Pedro. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Mazza, Osvaldo. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; ArgentinaFil: Vazquez, Elba Susana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaFil: de Siervi, Adriana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentin

The Effect of Stearic Acid on Breast Cancer Development and Progression

earate is an 18-carbon saturated fatty acid that is found in many foods in the western diet including beef and chocolate. Cell culture studies indicate stearate may have various anti-cancer properties including inhibition of cancer cell proliferation and invasion, morphological changes, and induction of apoptosis. Animal studies have found that dietary stearate delays tumor development and decreases tumor incidence. To date, many of the mechanisms underlying these processes are unclear. In this study, evidence is presented showing stearate induces morphological changes in breast cancer cells. Inhibition of de novo diacylglycerol (DAG) generation and subsequent protein kinase C (PKC) activation inhibits stearate-induced cell rounding. Further examination of the individual PKC isozymes with pharmacologic inhibitors indicates that PKC may be directly involved in stearate-induced cell rounding. Similar results were obtained with caspase-3 activity assays where stearate treatment appears to induce apoptosis of breast cancer cells in a manner dependent on DAG and PKC. Stearate induces apoptosis in a time and dose dependent manner through a pathway mediated by both the extrinsic and intrinsic cascades. In vivo, dietary stearate decreases primary tumor size in athymic nude mice injected in the mammary fat pad with MDA-MB-435 breast cancer cells. Stearate also inhibits metastasis to the lungs through a mechanism independent of primary tumor size. Future studies are necessary to elucidate the mechanisms underlying the dietary stearate-induced decrease in primary tumor size and inhibition of metastasis. Taken together, these results indicate stearate may be a potential preventative and/or adjuvant therapy for those at high risk for developing breast cancer

PREVENTION OF HORMONAL MAMMARY CARCINOGENESIS IN RATS BY DIETARY BERRIES AND ELLAGIC ACID

Breast cancer is the most frequently diagnosed cancer among women around the world. The hormone 17-estradiol (E2) is strongly implicated as a causative agent in this cancer. Since estrogen acts as a complete carcinogen, agents that interfere with the carcinogenic actions of E2 are required. Most agents effective against experimental mammary carcinogenesis have been employed as pure compounds disregarding the synergy that exists between several phytonutrients in a whole food. In these studies we have taken a unified approach, by employing a pure phytonutrient ellagic acid and whole foods that contain the phytonutrient at various levels berries, in the prevention of E2- induced mammary cancer in ACI rats. We have also used a tiered approach by screening several phytochemicals in vitro and implementing these results in both short- and long-term studies. Initially, several phytochemicals were tested as pure compounds against oxidative DNA damage induced by 4-hydroxy estradiol and CuCl2. Ellagic acid, was the most effective agent (andgt;98% reduction). In a short-term in vivo study, both dietary blueberry and strawberry (5% w/w), were ineffective in reducing the baseline oxidative DNA damage in the livers of CD-1 mice. However, red raspberry (5% w/w) was highly effective (50% reduction) and ellagic acid (400 ppm) was moderately effective (25% reduction). Further both diets up-regulated hepatic DNA repair genes in a similar fashion. In a long-term estradiol-induced mammary carcinogenicity study in ACI rats, dietary berries (2.5% w/w) and ellagic acid (400 ppm) reduced both tumor volume and tumors per animal to different extents (50-75%). One mechanism by which these dietary interventions inhibit mammary tumorigenesis may be via modulation of E2 metabolism, especially at the early stages of carcinogenesis. At 6 weeks after E2 treatment both berries and ellagic acid or berries alone significantly offset E2- induced changes in CYP1B1 and CYP1A1 expressions respectively. In addition, no toxicity or adverse effects are observed when rodents were fed either berries (1 - 5%) or ellagic acid (400 ppm). These data taken collectively support the possibility of using natural foods such as berries as an adjuvant to current pharmacological therapies in the prevention and treatment of breast cancer