Cancer PUFAs

Fat is a key component in the human diet. Research shows that excessive consumption of saturated fat negatively impacts several biomarkers of health while monounsaturated and n-3 PUFAs are beneficial to human health. Moreover, research shows that imbalanced dietary ratios of n-6 n-3 may lead to various health complications as well as disease progression while increased n-3 levels impart prevention and health promoting effects (Burghardt et al., 2010 Goodstine et al., 2003 Simopoulos, 2002 Wan et al., 2010). The American Heart Association recommends eating fatty fish meals at least twice a week due to their promising health and especially cardiovascular benefits. Here, we review some of the health benefits of n-3 PUFAs, due in part to their anti-inflammatory effects in cancer, cardiovascular diseases (CVDs), obesity, and other metabolic disorders. 

Cabanes, A., Wang, M., Olivo, S., Gustafsson, J., and Hilakivi-Clarke, L. (2003). Effect of n-3 polyunsaturated fatty acids (PUFAs) on breast cancer progression. Cancer Epidemiol. Biomarkers Prev. 12 (1305S). 

In a large trial (37) conducted in eight European countries— European Antioxidant Miocardial Infarction and Breast Cancer (EURAMIC) trial—the fatty acid composition, a-tocopherol, and /3-carotene levels were determined in adipose tissue of patients with acute Ml. The study supported the hypothesis that /3-carotene protects against Ml because it reduces the oxidation of PUFA. The concentration on adipose tissue was considered due to the dietary intake. 

The n-6 PUFAs have been shown to upregulate COX-2 expression,80 whereas n-3 PUFAs have been shown to suppress its expression in tumors,81,82 in association with decreased proliferation of cancer cells and reduced tumor angiogenesis.83 n-3 PUFAs have also been shown to suppress tumor growth via a COX-independent pathway.84 DHA, in comparison with LA, has also been shown to decrease the expression of other oncogenes implicated in tumor promotion including ras85 and bcl-2 expression,86 resulting in inhibition of mitosis and enhanced apoptosis of cancer cells, respectively. 

The n-3 PUFAs are reported to reduce expression of endothelial adhesion molecules VCAM-1, E-selectin, and ICAM-1, therefore influencing leukocyte-endothelial cell interactions and leukocyte migration across the endothelium. 105,106 Oxidized EPA has been shown to be a more potent inhibitor of leukocyte-endothelial interaction, in vitro and in vivo, than EPA.107 Since EFAs regulate intercellular adhesion, it has been speculated that the skin changes that are observed in EFA deficiency, may be due, at least in part, to damaged cell adhesion.108 n-3 PUFAs and GLA supplementation enhance E-cadherin expression in cancer cells and this possibly reduces the invasiveness of these cells.109... 

PUFAs are potent inhibitors of the HMG-CoA reductase enzyme and similar to statins are useful in the treatment of hyperlipidemias (99-102). Statins enhance plasma AA levels and decrease the ratio of EPA to AA significantly (100). This finding suggests that PUFAs mediate many actions of statins (103) and that this could be one mechanism by which they lower cholesterol levels. Statins and PUFAs have many overlap actions such as the inhibition of IL-6 and TNF-a production and NF-kB activation plus the ability to enhance eNO production thus, both possess anti-inflammatory actions and both are useful in atherosclerosis, coronary heart disease, osteoporosis, stroke, Alzheimer s disease, and inflammatory conditions such as lupus and cancer (3, 4, 94, 104-121). These similar and overlap actions strongly indicate that the molecular mechanisms of actions of statins and PUFAs are similar, if not identical. Furthermore, when a combination of statins and PUFAs are given together, a synergistic beneficial effect was seen in patients with combined hyperlipemia (122). 

To advance understanding of the dynamic influence of dietary lipids, research efforts are focusing on the importance of the balance between n-6 and n-3 fatty acids in the human diet. What is emerging is recognition that these PUFAs modulate eicosanoid biosynthesis in numerous tissues and cell types, alter signal transduction, and influence gene expression (87, 118). The effect of n-6 and n-3 PUFA on CVD, cancer and bone/joint health is related to the newer discoveries of how dietary PUFA impact health. 

The markets for ARA and DHA are now well established in Europe and the United Stated and are clearly being developed in Japan as well as in China. The next PUFA that appears likely to be produced is EPA, which could be used as a nutraceutical for over-the-counter sales or, more likely, as a possible pharmaceutical, as there have been numerous reports of its benefits for the treatment of various diseases and disorders. Such conditions as atherosclerosis, cancer, rheumatoid arthritis, psoriasis, bipolar disorder, schizophrenia, and Alzheimer s disease have all been said to have been improved or relieved by the oral administration of EPA, sometimes on its own, although sometimes with DHA (34, 70-72). EPA and DHA, of course, occur together in many fish oils, and when treatment with both these PUFAs is advocated, then the use of fish oils would seem to be the appropriate recommendation. 

E lipid-soluble antioxidant, prevents lipid oxidation of membranes, needed for healthy blood cells and tissues, blocks nitrosamine formation, protects PUFAs from autoxidation, important for normal immune fimction neuromuscular disorders, red blood ceU mpture (both uncommon) reduces risk of chronic disease (cardio-vascular, precancerous lesions, cancer), immunoenhancement, protec-tion from exercise-induced muscle injury, improves metaboHc control, re-duces risk of compHcations in diabetes... 

Furthermore, a diet with low contents of FA may be involved in the development of insulin resistance, which suggests that an appropriate dietary intake of n-3 PUFA is considered protective against metabolic syndrome [183]. In addition, diverse psyquiatric impairs (depression, bipolar disorders, schizophrenia, autism) and neurodegenerative diseases such as Alzheimer disease have been associated to decreased blood levels of n-3 HUFA. Besides, there are many examples about the use of pol)nmsaturated FA as drugs. Thus, EPA has shown efficacy as adjunctive treatment, and in some cases as the only treatment in several psyquiatric disorders [184]. It is suggested that the potential of n-3 FA to prevent recurrence and metastasis of mammary cancer when used in adjuvant therapy is associated with a n-6 to n-3 ratio lower than 2 1 [185], On the other hand, fish intake is considered as a protective factor for preventing prostate cancer in addition, in humans low levels of ALA in mammary adipose tissue are associated with an increased risk of breast cancer in women [186]. 

Over the past 50 yr, there has been an increase in diabetes, heart disease and cancer, thoughtto be caused, in part, by changes in environmental factors. The nutrients we eat may be the most influential environmental stimuli, and fat is a strong determinant of cell differentiation, growth, and metabolism. Although the effects of n-3 PUFAs on several behavioral indices have been widely reported, there is still much work to be done if we are to understand the mechanism by which this family of fatty acids exerts its many actions. 

Two polyunsaturated fatty acids (PUFAs), linoleic and a-linolenic acid, are necessary for good health. Referred to as essential fatty acids (EFAs) because they cannot be manufactured by the body, but depend on being provided by nutritional intake, EFAs have beneficial effects when available in moderation. Excesses of the otherwise beneficial fatty acids may, however, exert harmful effects, with high intakes of saturated and hydrogenated fats being linked to an increase in a number of health risks, including degenerative diseases, cardiovascular disease, cancer, and diabetes. 

These fatty acids play an important role also in the amelioration of autoimmune diseases, such as arthritis, and in the inhibition of the rapid proliferation of cancer cells. However, PUFA in membrane lipids are vulnerable to free radical-initiated oxidation, generated by xenobiotics or normal aerobic cellular metabolism that results in the formation of lipid peroxides [84]. 

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