Anticancer effects of n-3 EPA and DHA and their endocannabinoid derivatives on breast cancer cell growth and invasion.

The anticancer effects of the omega-3 long chain polyunsaturated fatty acids (LCPUFA), EPA and DHA may be due, at least in part, to conversion to their respective endocannabinoid derivatives, eicosapentaenoyl-ethanolamine (EPEA) and docosahexaenoyl-ethanolamine (DHEA). Here, the effects of EPEA and DHEA and their parent compounds, EPA and DHA, on breast cancer (BC) cell function was examined. EPEA and DHEA exhibited greater anti-cancer effects than EPA and DHA in two BC cells (MCF-7 and MDA-MB-231) whilst displaying no effect in non-malignant breast cells (MCF-10a).

Circulating levels of angiogenesis-related growth factors in breast cancer: A study to profile proteins responsible for tubule formation.

The present study exploited a versatile in vitro endothelial cell/fibroblast co-culture cell system to investigate the association between angiogenesis and breast cancer by comparing the capacity of plasma from women with breast cancer and age-matched controls, to influence tubule formation and modulate angiogenesis in vitro, and to identify plasma circulating factors which might be responsible. Plasma from women with breast cancer (n=8) (added on day 7 after co-culture establishment) significantly increased tubule formation by 57% (P<0.01) when compared to cultures grown in culture medium lacking in vascular endothelial growth factor (VEGF) and fetal bovine serum (FBS), whereas plasma from controls (n=8) did not.

Cannabinoids and omega-3/6 endocannabinoids as cell death and anticancer modulators.

Cannabinoids-endocannaboids are possible preventatives of common diseases including cancers. Cannabinoid receptors (CB(½), TRPV1) are central components of the system. Many disease-ameliorating effects of cannabinoids-endocannabinoids are receptor mediated, but many are not, indicating non-CBR signaling pathways.

Cannabinoid receptor-dependent and -independent anti-proliferative effects of omega-3 ethanolamides in androgen receptor-positive and -negative prostate cancer cell lines.

The omega-3 fatty acid ethanolamides, docosahexaenoyl ethanolamide (DHEA) and eicosapentaenoyl ethanolamide (EPEA), displayed greater anti-proliferative potency than their parent omega-3 fatty acids, docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), in LNCaP and PC3 prostate cancer cells. DHEA and EPEA activated cannabinoid CB(1) and CB(2) receptors in vitro with significant potency, suggesting that they are endocannabinoids. Both LNCaP and PC3 cells expressed CB(1) and CB(2) receptors, and the CB(1)- and CB(2)-selective antagonists, AM281 and AM630, administered separately or together, reduced the anti-proliferative potencies of EPEA and EPA but not of DHEA or DHA in PC3 cells and of EPA but not of EPEA, DHEA or DHA in LNCaP cells.

Enhancing cytotoxic therapies for breast and prostate cancers with polyunsaturated fatty acids.

The role of omega-3 and omega-6 fatty acids has been extensively studied in most of the human malignancies including breast, colon, prostate, pancreas, and stomach cancers. In particular, the role of omega-3 and omega-6 fatty acids in carcinogenesis has been extensively investigated in epidemiological, laboratory cell culture studies and studies in vivo in animal. Findings from these studies suggest that omega-3 and omega-6 fatty acids are cytotoxic in different cancers and act synergistically with cytotoxic drugs.

Plant phenolics in the prevention and treatment of cancer.

Epidemiological studies indicate that populations consuming high levels of plant derived foods have low incidence rates of various cancers. Recent findings implicate a variety of phytochemicals, including phenolics, in these anticancer properties. Both monophenolic and polyphenolic compounds from a large variety of plant foods, spices and beverages have been shown to inhibit or attenuate the initiation, progression and spread of cancers in cells in vitro and in animals in vivo.

Docosahexaenoic acid enhances the efficacy of docetaxel in prostate cancer cells by modulation of apoptosis: the role of genes associated with the NF-kappaB pathway.

Background: Evidence is growing for beneficial interactions between omega-3 fatty acids from fish and chemotherapy agents in certain human cancers. Evidence for similar effects in prostate cancer is lacking. We investigated the effects of docosahexaenoic acid (DHA-22:6n-3), a component of fish oil, on the cytotoxicity of docetaxel in prostate cancer cells.

Effect of a conjugated linoleic acid and omega-3 fatty acid mixture on body composition and adiponectin.

This study aimed to determine the effect of supplementation with conjugated linoleic acids (CLAs) plus n-3 long-chain polyunsaturated fatty acids (n-3 LC-PUFAs) on body composition, adiposity, and hormone levels in young and older, lean and obese men. Young (31.4+/-3.

Cytoprotective effects of phenolic antioxidants and essential fatty acids in human blood monocyte and neuroblastoma cell lines: surrogates for neurological damage in vivo.

Background: Oxidative stress is implicated in the development of a range of neurological diseases. There is increasing interest in the neuroprotective efficacy of antioxidants in modulating such processes with at least one polyphenolic being tested as a prophylactic in Alzheimer's disease. Beneficial effects of adjunctive n-3 polyunsaturated fatty acids with combined intakes of vitamin C and E on both the positive and negative symptoms of schizophrenia have been reported.

Potentiation of the anti-tumour effect of docetaxel by conjugated linoleic acids (CLAs) in breast cancer cells in vitro.

Response rates of tumours to docetaxel (DOCT) are 45-60% in advanced breast cancer but problems associated with side effects, drug resistance and high costs occur. Conjugated linoleic acids (CLAs) also have anti-tumorigenic activity that elicits similar changes in oncogene expression to DOCT and could augment DOCT efficacy. CLA isomers appear to differ in cytotoxicity toward cancer cells.

Age-related increases in circulating inflammatory markers in men are independent of BMI, blood pressure and blood lipid concentrations.

Objective: To examine whether age-related increase in concentrations of circulating inflammatory mediators is due to concurrent increases in cardiovascular risk factors or is independent of these.

Methods And Results: Cytokines (IL-6, IL-18), chemokines (6Ckine, MCP-1, IP-10), soluble adhesion molecules (sICAM-1, sVCAM-1, sE-selectin) and adipokines (adiponectin) were measured in the plasma of healthy male subjects aged 18-84 years (n=162). These were related to known cardiovascular risk factors (age, BMI, systolic and diastolic blood pressure, plasma total cholesterol, LDL cholesterol, HDL cholesterol and triacylglycerol concentrations) in order to identify significant associations.

Age- and dose-dependent effects of an eicosapentaenoic acid-rich oil on cardiovascular risk factors in healthy male subjects.

Supplementation with fish oils, rich in n-3 polyunsaturated fatty acids, modifies cardiovascular risk factors. However, dose-response relationships are poorly defined and whether similar effects are seen in young and older subjects is not known. This study determined the effect of supplementing the diet of young and older male subjects with different amounts of an eicosapentaenoic acid (EPA)-rich oil.

Cytokine-induced monocyte adhesion to endothelial cells involves platelet-activating factor: suppression by conjugated linoleic acid.

Monocyte-endothelium interaction is key to many acute and chronic inflammatory diseases. We have investigated the factors regulating monocyte attachment to cytokine-activated human umbilical vein endothelial cells (HUVEC) and the modulatory effect of the polyunsaturated fatty acid (PUFA), conjugated linoleic acid (CLA) in this process. Both TNF-alpha and IL-1beta induced HUVEC platelet-activating factor (PAF) production and PAF was required for subsequent firm THP-1 monocyte adhesion since it was inhibited by both PAF receptor antagonists (BN-52021 or CV-6209) and a PAF synthesis inhibitor (sanguinarine).

Induction of apoptosis and inhibition of NF-kappaB activation in human prostate cancer cells by the cis-9, trans-11 but not the trans-10, cis-12 isomer of conjugated linoleic acid.

Background: Conjugated linoleic acids (CLAs) have anti-tumorigenic properties in animal models and anti-proliferative effects on cancer cells in vitro. Previous studies have shown that the NF-kappaB pathway is involved regulating anti-apoptotic gene expression. The present study investigated the effects of CLAs (cis-9, trans-11, and trans-10, cis-12 isomers and a 50:50 mixture) on apoptosis and NF-kappaB activation in LNCaP cells.

Olive oil and modulation of cell signaling in disease prevention.

Epidemiological studies show that populations consuming a predominantly plant-based Mediterranean-style diet exhibit lower incidences of chronic diseases than those eating a northern European or North American diet. This observation has been attributed to the greater consumption of fruits and vegetables and the lower consumption of animal products, particularly fat. Although total fat intake in Mediterranean populations can be higher than in other regions (ca.

Conjugated linoleic acids: are they beneficial or detrimental to health?

Conjugated linoleic acids (CLAs) comprise a family of positional and geometric isomers of linoleic acid (18:2n-6; LA) that are formed by biohydrogenation and oxidation processes in nature. The major dietary sources of these unusual fatty acids are foods derived from ruminant animals, in particular dairy products. The main form of CLA, cis-9, trans-11-18:2, can be produced directly by bacterial hydrogenation in the rumen or by delta-9 desaturation of the co-product vaccenic acid (trans-11-18:1) in most mammalian tissues including man.

Conjugated linoleic acid inhibits proliferation and modulates protein kinase C isoforms in human prostate cancer cells.

Prostate cancer is the second most common cancer in men. The disease etiology is poorly understood, but diet and lifestyle are contributory factors. Conjugated linoleic acids (CLAs), naturally occurring fatty acids in ruminant food products, have antitumor properties in animal models of cancer and antiproliferative effects on cancer cells in vitro.

Conjugated linoleic acids (CLAs) decrease prostate cancer cell proliferation: different molecular mechanisms for cis-9, trans-11 and trans-10, cis-12 isomers.

The aims of this study were to examine the anti-proliferative effects of different concentrations of a commercial preparation of conjugated linoleic acids (CLA) mixture of isomers [cis-9, trans-11 CLA (c9,t11 CLA): trans-10, cis-12 CLA (50:50)] and their constituent isomers on PC-3, a human prostatic carcinoma cell line, and to study their effects on gene expression (mRNA and protein levels) of different enzymes and oncoproteins involved in oncogenesis and progression of prostate cancer. This includes pathways for arachidonic acid metabolism [cyclooxygenase 1 (COX-1), 2 (COX-2) and 5-lipoxygenase (5-LOX)], apoptosis (bcl-2) and cell cycle control (p21(WAF/Cip1)). Our results indicate a significant decrease in PC-3 proliferation elicited by CLA, although with high variability between isomers.

Regulation of selenoprotein GPx4 expression and activity in human endothelial cells by fatty acids, cytokines and antioxidants.

Phospholipid hydroperoxide glutathione peroxidase (GPx4) is the only antioxidant enzyme known to directly reduce phospholipid hydroperoxides within membranes and lipoproteins, acting in conjunction with alpha-tocopherol to inhibit lipid peroxidation. Peroxidation of lipids has been implicated in a number of pathophysiological processes, including inflammation and atherogenesis. We investigated the relative positive and negative effects of specific polyunsaturated fatty acids (PUFAs) and inflammatory cytokines on the activity and gene expression of the selenium-dependant redox enzyme GPx4.

Polyunsaturated fatty acids and gene expression in mammalian systems.

Over the last 30 years it has become apparent that specific dietary fatty acids are capable of regulating, either directly or indirectly through various signal pathways, the expression of numerous genes, either positively or negatively. Such nutrient-gene interactions have important effects on cell metabolism, differentiation and growth, and ultimately on disease processes. The present review describes some of the more important fatty acid-gene interactions in relation to health and disease in mammalian species, and focuses on the underlying cell signal mechanisms, including various transcription factors, affected by fatty acids and some of their oxygenated derivatives, e.