Differential Potentiation of Retinoic Acid Effects against Human Breast Cancer Cells by Unsaturated Fatty Acids.

Retinoic acid (RA) and unsaturated fatty acids (UFA) are proposed as nutritional anticancer agents. Nonetheless, the activity of their combination on human breast cancer needs further study. Our aim was to evaluate this activity on the MCF-7 and ZR-75-1 cell lines treated with 1 µM RA and 50 µM of γ-linoleic (GLA, ω-6), eicosapentaenoic (EPA, ω-3), oleic (OA, ω-9), or eicosatrienoic (ETA, ω-9) acids. The following cellular responses were compared by ANOVA and Fisher test (P < 0.05): fatty acids, E-cadherin, actin (differentiation), conjugated dienes, γ-glutamyltranspeptidase activity (stress), and viability, which were correlated by partial least squares regression. Although both cell lines responded differentially, RA modified unsaturated fatty acids, increased differentiation, reduced γ-glutamyltranspeptidase, and viability. RA differentiating activity on ZR-75-1 was morphologically enhanced by UFA. Stress induction with γ-glutamyltranspeptidase decrease and conjugated dienes was promoted by ETA in MCF-7, and EPA and OA in ZR-75-1. RA-related reduced viability was potentiated by EPA and OA in both lines. GLA was less active. Therefore, unsaturated fatty acids (ω-3/ω-9) potentiated the multitarget retinoic acid activity against these human breast cancer cells.

Modulation of Fatty Acids and Interleukin-6 in Glioma Cells by South American Tea Extracts and their Phenolic Compounds.

Dietary phenolic compounds are plant metabolites with beneficial effects on the central nervous system. Thus, our aim was to identify anti-inflammatory compounds from South American plants on glia, which regulates neuro-immune response. The compounds were extracted from Lantana grisebachii (LG), Aspidosperma quebracho-blanco (AQB), and Ilex paraguariensis (IP) teas and identified by HPLC-DAD-MS. Extracts (0-200 µg/ml) were tested on human T98-G and rat C6 glioma lines. Cellular viability (by the resazurin assay), fatty acid profile (by gas chromatography) and pro-inflammatory interleukin-6 release (IL-6 by ELISA) were determined. Data were analyzed by partial least-square regression to discriminate bioactive compounds. Twenty-one compounds were determined in LG, mainly iridoids, which were linked to ω-3 and ω-6 polyunsaturated fatty acids, but not to IL-6 release. Thirty-one compounds were found in AQB, mostly hydroxybenzoic derivatives, which were positively related to IL-6 release. Twenty-three compounds were identified in IP, including caffeoylquinic derivatives and mainly chlorogenic acid. They increased the ω-7 palmitoleic fatty acid, which was related to IL-6 decrease. These results enhances phytochemical knowledge of widely available plants, and suggest the lipid-related anti-inflammatory activity of IP phenolic compounds, which give nutritional relevance to the tea.

Delay of Lung Adenocarcinoma (LAC-1) Development in Mice by Dietary Oleic Acid.

Lung cancer is the leading cause of death by cancer, and is a major sanitary concern worldwide. Some nutrients, such as ω-9 fatty acids, have been proposed as anticancer agents. Thus, an olein-enriched diet was assayed in a murine model of lung adenocarcinoma (LAC-1) to evaluate neoplastic and paraneoplastic evolution in BALB/c mice. The organic assimilation of dietary fatty acids was confirmed in liver by gas chromatography. This experimental oleic acid-containing diet increased animal survival and tumour latency (analysed by the Kaplan-Meier method), improving neoplastic evolution and general status, with weak effects on the paraneoplastic syndrome (thymus atrophy, splenomegaly, splenocyte response to mitogen, blood anaemia, and leucocytosis). Tumour lipid oxidation was not involved. Thus, diet enrichment with olein, a natural source of the ω-9 oleic acid, significantly delayed progression of LAC-1 and increased tumour latency and mice survival. These results support its use in nutritional management of cancer, with further studies being encouraged.

Increased dietary levels of α-linoleic acid inhibit mammary tumor growth and metastasis.

OBJECTIVE: The aim of this study was to determine whether α-linolenic acid (ALA ω-3 fatty acid) enriched diet affects growth parameters when applied to a syngeneic model of mammary carcinoma. MATERIALS AND METHODS: BALB/c mice were divided and fed with: 1) a chia oil diet, rich in ALA or 2) a corn oil diet, rich in linoleic acid (LA ω-6 fatty acid). Mice were subcutaneously inoculated with a tumor cell line LM3, derived from a murine mammary adenocarcinoma. RESULTS: After 35 days, tumor incidence, weight, volume and metastasis number were lower in the ALA-fed mice, while tumor latency time was higher, and the release of pro-tumor metabolites derived from ω-6 fatty acids decreased in the tumor. Compared to the control group, a lower number of mitosis, a higher number of apoptotic bodies and higher T-lymphocyte infiltration were consistently observed in the ALA group. An ALA-rich diet decreased the estrogen receptor (ER) α expression, a recognized breast cancer promotor while showing an opposite effect on ERß in tumor lysates. CONCLUSION: These data support the anticancer effect of an ALA-enriched diet, which might be used as a dietary strategy in breast cancer prevention.

Characterization of a murine lung adenocarcinoma (LAC1), a useful experimental model to study progression of lung cancer.

Lung cancer is one of the most important avoidable causes of death around the world, the most widespread carcinoma, with a very poor prognosis, and is the leading cause of cancer death in both developed and developing countries. We report morphological and biological behavior characteristics of a tumor that arose in only one BALB/c mouse of an experimental group treated with urethane, a chemical lung-tumorigenic agent. Morphological and immunochemical analysis indicated phenotypic compatibility with a lung adenocarcinoma. The tumor was named LAC1 (lung adenocarcinoma 1). Implant success in eight LAC1-bearing mice generations was 100%, with a fast evolution (58 survival days) and good metastatic capacity (41% of animals with metastases). The tumor induced a paraneoplastic syndrome characterized by anemia, neutrophilia, cachexia, splenomegaly and thymic atrophy. The lymphoproliferation to Con A was altered in tumor-bearing mice. This lung adenocarcinoma may be a useful experimental model for studying tumor progression, paraneoplastic syndromes and immunology in carcinogenic studies.

Anti-breast cancer activity of curcumin on the human oxidation-resistant cells ZR-75-1 with gamma-glutamyltranspeptidase inhibition.

Since curcumin, a polyphenol extracted from the rhizomes of Curcuma longa L. (Zingiberaceae), has been proposed for breast cancer chemoprevention, the aim of the present work was to determine if it had anti-tumour effects on mammary cells which are resistant to oxidative damage. ZR-75-1 cells were treated with curcumin and copper(II) sulphate in order to evaluate cell death and gamma-glutamyltranspeptidase (GGTP) activity. Curcumin was cytotoxic in a dose-dependent manner (loss of viability with lactate-dehydrogenase release) with apoptotic effects on ZR-75-1 cells. Also, curcumin displayed an antioxidant effect only on the copper-oxidized cells. The GGTP activity was decreased in a dose-dependent manner by curcumin, with the changes in this parameter accounting for neoplastic inhibition (direct relation between the enzyme activity and cellular viability). Summing up, our results suggest that curcumin induced apoptosis in ZR-75-1 with an antioxidant activity performed on those treated with copper(II) sulphate, which should be explored more thoroughly with the involvement of the GGTP enzyme activity as biomarker of their malignancy.

Omega-3 and Omega-6 salivary fatty acids as markers of dietary fat quality: A cross-sectional study in Argentina.

The use of saliva for analyzing biological compounds has recently been expanded. The aim of this study was to analyze the correlation between specific dietary sources of n3 and n6 fatty acids (FA) and their salivary levels to evaluate their role as intake markers. Seventynine healthy volunteers were included. A validated food frequency questionnaire was used for data collection and Interfood v.1.3 software was employed to quantify food intake. Salivary samples were collected following international standards and FA profile was determined by gas liquidchromatography. Multiple linear regression analyses were performed for dependent variables (salivary FA profile) to detect independent associations with n3 and n6 FA food source intake, adjusted by age, gender, bodymass index, total energy intake, regular exercise, alcohol intake and smoking. Salivary concentrations of alphalinolenic acid (ALA) 18:3 n3 were significantly associated with nuts intake (ß=0.05, 95% CI 0.020.07, p=0.04). Salivary concentrations of linoleic acid (LA) 18:2 n6 and arachidonic acid (AA) 20:4 n6 were associated with the intake of n6 vegetable oils and red meat, cold meat and viscera (ß=0.80, 95% CI 0.060.09 p=0.03; ß=0.40, 95% CI 0.300.50, p=0.02, respectively). This study supports the hypothesis that salivary concentrations of n3 and n6 FA are related to food intake. Monitoring dietary FA though salivary markers is relevant for nutrition epidemiology and for prevention and management of several diseases related to fat intake.

El uso de biomarcadores salivales está en continua expansión. El objetivo de este estudio fue analizar la asociación entre fuentes alimentarias de ácidos grasos (AG) n3 y n6 y sus concentraciones salivales como marcador de ingesta. Parti ci paron 79 voluntarios sanos. Se aplicó un cuestionario validado de frecuencia de consumo alimentario y el software Interfood v.1.3 para su procesa miento. Las muestras saliva les se recogieron según estándares internacionales y se determinó el perfil de AG salivales por cromatografía gaseosa. Se desarrolló un modelo de regresión lineal múltiple ajustado por sexo, edad, índice de masa corporal, valor energético total, actividad física, consumo de tabaco y alcohol para analizar la asociación entre el perfil de AG salivales y la ingesta de alimentos fuente de AG n3 y n6. Las concentraciones salivales del AG alfalinolénico (ALA) 18:3 n3 se asociaron positivamente con la ingesta de nueces (ß=0.05, IC 95% 0.020.07, p=0.04), mientras que las concentraciones salivales de ácido linoleico (AL) 18:2 n6 y araquidónico (AA) 20:4 n6 se asociaron con el consumo de aceites ricos en n6 (ß=0.80, 95% IC 0.060.09 p=0.03) y de carnes rojas, fiambres y embutidos y vísceras, (ß=0.40, IC 95% 0.300.50, p=0.02). De acuerdo a estos resultados, las concen traciones salivales de AG n3 y n6 se relacionan a la ingesta de sus alimentos fuente. El monitoreo de la ingesta lipídica a través de biomarcadores salivales constituye un aporte a la epidemiología nutricional y a la prevención y tratamiento de patologías vinculadas a la ingesta de grasas.

Influence of diets varying in lipid and protein content on the histopathologic variety of murine salivary gland tumors induced by 9,10-dimethyl-1,2-benzanthracene (DMBA).

The purpose of this study was to analyze the influence of diets varying in lipids and proteins on the histopathologic variety of murine salivary tumors induced by DMBA. 117 BALB/c mice were assigned to experiments one (E1: lipids, males) and two (E2: proteins, males and females), E1 comprising Soy oil (SO); Corn oil (CO, control); Fish oil (FO) and Olein (O) groups and E2, soy protein (SP) and casein (C) groups. Tumors were induced by DMBA and the animals were sacrificed at week 13- post-induction. Tumor volume was calculated. Tumor sections were stained with H-E for histopathologic evaluation. No significant association was found between tumor volume and dietary condition (p > 0.05). In E1, FO animals developed mainly carcinomas (C) (58.8%), the sarcomas (S) and carcinosarcomas (CS) being especially of high-grade type (tumors < 600 mm3). In E2, SP animals developed mainly C (55.6%). Although no significantly different (p > 0.05), S and C were more frequent in female and male mice, respectively. In both E1 and E2, the biggest tumors (> 600 mm3) were mainly high-grade S (87.5%-80%). Dietary fat and soy protein appear to influence the tumor histopathology and thus its prognosis.

Effects of soy oil on murine salivary tumorigenesis.

Dietary fat influences dimethylbenzanthracene (DMBA)-induced tumorigenesis of several organs, including the salivary glands. There is not enough evidence to suggest that soy oil could also affect growth of salivary tumors. The main purpose of this work therefore was to study the effects of dietary soy oil on macroscopic parameters of chemically induced murine salivary gland tumors. Eighty BALB/c male mice were assigned to four groups: soy oil (SO), corn oil (CO, control), fish oil (FO) and olein (O). Two weeks later, tumors were induced by 9,10-dimethyl-1,2-benzanthracene (DMBA). At the 13th post-injection week, the animals were sacrificed. In vivo tumor diameter, gland volume (total resected mass), tumor volume (microscopically measured), tumor remission and tumor histopathology were analyzed. The initial in vivo tumor diameter, gland and tumor volume were significantly greater in soy oil than in fish oil group. 26.7% of animals on the soy oil diet showed tumor remission. Sarcomas were more often found in the SO group, carcinomas in FO and the mixed-type tumors both in SO and CO groups. This study shows that the soy oil treatment resulted in larger tumors, some of which later became undetectable. It is necessary to further investigate these divergent results.

[Proliferation and apoptosis in tongue epithelium of mice bearing salivary tumors induced by dimetilbenzantraceno (DMBA) and modulated by dietary lipids]. / Proliferación y apoptosis en epitelio lingual de ratones con tumores salivales inducidos por dimetilbenzantraceno (DMBA) y modulados por lípidos dietarios.

INTRODUCTION: According to the concept of field defects during the carcinogenesis process, excessive epithelial proliferation/apoptosis may exist in areas near tumors. Proliferation or apoptosis could be modified by dietary lipids. PURPOSE: The present study was designed to analyze proliferation and apoptosis in tongue epithelium of mice fed diets based on different lipids followed by induction of salivary tumors with DMBA. MATERIALS AND METHODS: Forty-five days after weaning, ten BALB/c mice were assigned to two diets: corn oil (CO) and fish oil (cod liver, FO). Two weeks later, DMBA was injected in the submandibular area. Animals were sacrificed at the 13th post-injection week. Samples of tongue were fixed in formalin-ethanol and immunohistochemically stained for proliferation (Ki-67) and apoptosis (Bax). By light microscopy, the number of nuclei positive for these markers were counted out of three-hundred total interphase cells both in dorsal and in ventral tongue surfaces. Results were analyzed through Analysis of Variance and t Test. RESULTS: Cell proliferation was greater in dorsal than in ventral tongue surfaces (p < 0.0001) with no diet difference. Apoptosis was significantly greater in mice fed FO than CO, particularly in tongue dorsal epithelia (p < 0.018). CONCLUSIONS: This study shows that FO diet induces higher levels of apoptosis in tongue epithelia suggesting a tissue defensive mechanism when exposed to a carcinogenic-tumoral agent.

Omega-3 and Omega-6 salivary fatty acids as markers of dietary fat quality: a cross-sectional study in Argentina

The use of saliva for analyzing biological compounds has recently been expanded. The aim of this study was to analyze the correlation between specific dietary sources of n3 and n6 fatty acids (FA) and their salivary levels to evaluate their role as intake markers. Seventynine healthy volunteers were included. A validated food frequency questionnaire was used for data collection and Interfood v.1.3 software was employed to quantify food intake. Salivary samples were collected following international standards and FA profile was determined by gas liquidchromatography. Multiple linear regression analyses were performed for dependent variables (salivary FA profile) to detect independent associations with n3 and n6 FA food source intake, adjusted by age, gender, bodymass index, total energy intake, regular exercise, alcohol intake and smoking. Salivary concentrations of alphalinolenic acid (ALA) 18:3 n3 were significantly associated with nuts intake (ß=0.05, 95% CI 0.020.07, p=0.04). Salivary concentrations of linoleic acid (LA) 18:2 n6 and arachidonic acid (AA) 20:4 n6 were associated with the intake of n6 vegetable oils and red meat, cold meat and viscera (ß=0.80, 95% CI 0.060.09 p=0.03; ß=0.40, 95% CI 0.300.50, p=0.02, respectively). This study supports the hypothesis that salivary concentrations of n3 and n6 FA are related to food intake. Monitoring dietary FA though salivary markers is relevant for nutrition epidemiology and for prevention and management of several diseases related to fat intake (AU)

El uso de biomarcadores salivales está en continua expansión. El objetivo de este estudio fue analizar la asociación entre fuentes alimentarias de ácidos grasos (AG) n3 y n6 y sus concentraciones salivales como marcador de ingesta. Parti ci paron 79 voluntarios sanos. Se aplicó un cuestionario validado de frecuencia de consumo alimentario y el software Interfood v.1.3 para su procesa miento. Las muestras saliva les se recogieron según estándares internacionales y se determinó el perfil de AG salivales por cromatografía gaseosa. Se desarrolló un modelo de regresión lineal múltiple ajustado por sexo, edad, índice de masa corporal, valor energético total, actividad física, consumo de tabaco y alcohol para analizar la asociación entre el perfil de AG salivales y la ingesta de alimentos fuente de AG n3 y n6. Las concentraciones salivales del AG alfalinolénico (ALA) 18:3 n3 se asociaron positivamente con la ingesta de nueces (ß=0.05, IC 95% 0.020.07, p=0.04), mientras que las concentraciones salivales de ácido linoleico (AL) 18:2 n6 y araquidónico (AA) 20:4 n6 se asociaron con el consumo de aceites ricos en n6 (ß=0.80, 95% IC 0.060.09 p=0.03) y de carnes rojas, fiambres y embutidos y vísceras, (ß=0.40, IC 95% 0.300.50, p=0.02). De acuerdo a estos resultados, las concen traciones salivales de AG n3 y n6 se relacionan a la ingesta de sus alimentos fuente. El monitoreo de la ingesta lipídica a través de biomarcadores salivales constituye un aporte a la epidemiología nutricional y a la prevención y tratamiento de patologías vinculadas a la ingesta de grasas (AU)

Influence of diets varying in lipid and protein content on the histopathologic variety of murine salivary gland tumors induced by 9, 10-dimethyl-1, 2-benzanthracene (DMBA) / Influencia de dietas de diferente contenido lipídico y proteico sobre variantes histopatológicas de tumores de glándulas salivares murinos inducidos con 9, 10-dimethyl-1, 2-benzathraceno (DMBA)

The purpose of this study was to analyze the influence of diets varying in lipids and proteins on the histopathologic variety of murine salivary tumors induced by DMBA. 117 BALB/c mice were assigned to experiments one (E1: lipids, males) and two (E2: proteins, males and females), E1 comprising Soy oil (SO); Corn oil (CO, control); Fish oil (FO) and Olein (O) groups and E2, soy protein (SP) and casein (C) groups. Tumors were induced by DMBA and the animals were sacrificed at week 13- post-induction. Tumor volume was calculated. Tumor sections were stained with H-E for histopathologic evaluation. No significant association was found between tumor volume and dietary condition (p > 0.05). In E1, FO animals developed mainly carcinomas (C) (58.8%), the sarcomas (S) and carcinosarcomas (CS) being especially of high-grade type (tumors < 600 mm3). In E2, SP animals developed mainly C (55.6%). Although no significantly different (p > 0.05), S and C were more frequent in female and male mice, respectively. In both E1 and E2, the biggest tumors (> 600 mm3) were mainly high-grade S (87.5%-80%). Dietary fat and soy protein appear to influence the tumor histopathology and thus its prognosis.

El objetivo de este estudio fue analizar la influencia de dietas con diferente contenido de lípidos y proteínas sobre la variedad histopatológica de tumores salivares murinos inducidos por DMBA. Se asignaron 117 ratones BALB/c a los experimentos uno (E1: lípidos, machos) y dos (E2: proteínas, machos y hembras). E1 comprendió a los grupos aceite de soja (AS), aceite de maíz (AM, control), aceite de pescado (AP) y oleína (O), en tanto E2 incluyó a los grupos preteína de soja (PS) y caseína (C). Los tumores fueron inducidos por DMBA y los animales fueron sacrificados a la 13ª semana post-inducción. Se calculó el volumen tumoral. Los cortes de tumor fueron coloreados con Hematoxilina-Eosina para su evaluación histopatológica. No se encontró asociación entre volumen tumoral y condición dietaria (p>0.05). En E1, los animales del grupo AP desarrollaron principales carcinomas (C) (58,8%), en tanto que los sarcomas (S) y carcinosarcomas (CS) fueron de alto grado (tumores<600 mm³). En el E2, los animales del grupo PS desarrollaron principalmente C (55.6%). Aunque la diferencia no fue significativa (p>0.05), S y C fueron más frecuentes en ratones hembras y machos, respectivamente. Tanto el E1 com en E2, los tumores más voluminosos (> 600 mm³) fueron principalmente de alto grado (87.5%-80%) Los lípidos y la proteína de soja de la dieta parecen influenciar la histopatología de los tumores y, en consecuencia, su pronóstico.