Benefits in oncology. Mechanism of action

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1 Mechanism of action The word cancer refers to a number of different diseases that share a common trait: the rapid, unrestrained growth and spread of cells that can invade and destroy surrounding tissues, as well as distant ones. A normal cell can be transformed and grow out of control due to different risk factors that increase the likelihood of neoplastic disease. The relative proportions of fatty acids in cell membranes and cell type are the primary factors involved in the regulation of eicosanoid compounds production. Prostaglandin E2 (PGE2), leukotriene B4 (LTB4), thromboxane A2 (TXA2) and 12-hydroxyeicosatetraenoic acid are positively associated with cancer; omega-3 fatty acids can reduce cancer risk by competitively inhibiting them. To this effect, it is important to note that the power of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) is five times greater than that of alpha-linolenic acid and that the efficiency of conversion of alpha-linolenic acid to EPA and DHA is relatively low, especially in cancer cells. PPARs (peroxisome proliferator-activated receptors) are members of the nuclear receptor supergene family that consists of three isoforms: PPARa, PPARd/ß y PPARγ (which has three variants γ1, γ2 y γ3) that heterodimerize with the RXR nuclear receptor (9-cis-retinoic acid). These transcription factors are involved in the regulation of lipid metabolism and homeostasis, and they also modulate cell proliferation and differentiation. PPARa y PPARγ

2 activation is associated with the anticancer effects of omega 3 fatty acids. Omega-3 fatty acids have the ability to slow the growth of human cancer cells and strengthen the immune system of people with different types of cancer. Intake of omega-3 fatty acids also helps to decrease the mobility of cancer cells, thereby reducing the risk of invasion and metastasis in cancer patients. This is important because most cancer-related deaths are caused by secondary tumors caused by metastasis. Omega-3 fatty acids have anticancer effects in breast and colon cancer, leukemia and cutaneous malignant melanoma because they stop the growth of cancer cells. That is why it is very important to get the right amount, especially as we know that 80% of malignant tumors are due to environmental factors and lifestyle choices, which means that many cancers could be prevented. Eating omega 3 fatty acids makes it possible to reduce the dose, time and cycles of chemotherapy, and therefore to improve the quality of life of cancer patients. Pratt et al. reported that in various types of cancer (pancreas, prostate, jejunum, colorectal, lung, breast and others) with and without metastasis, plasma phospholipid concentrations of omega-3 fatty acids and omega-3 to omega-6 fatty acid ratios were abnormally low, especially in those patients with low body mass index and after receiving chemotherapy. Prospective studies have shown that in countries where fish intake is highest (between 0.5 and 1.5 g per day of omega 3 fatty acids), the relative risk for breast cancer (30%) and for prostate cancer (60%) is significantly lower. Furthermore, for every extra 0.5 g of omega-3 fatty acids added to the diet per day, the risk for metastasis decreases by 24%. Phase I clinical studies have established that the maximum tolerable daily intake of omega 3 fatty

3 acids is approximately 0.2 g per kg of body weight. Types of cancer Breast cancer The fatty acid synthase (FAS) is the regulating enzyme for the de novo fatty acid biosynthesis. Hyperactivity and overexpression of FAS (oncogenic antigen-519) in some particularly aggressive breast carcinomas has been described, which suggests the existence of FAS-dependent neoplastic lipogenesis. Studies in human SK-Br3 breast cancer cells show that DHA can reduce FAS expression by 37%. Omega-3 fatty acids can enhance the cytotoxic effects of some drugs used to fight breast cancer (paclitaxel, cerulenin, doxorubicin and cisplatin) as they increase the drugs uptake by cancer cells and act to overcome the cells resistance to chemotherapy. Some studies have shown the importance of omega 3 fatty acids in the efficacy of mitoxantrone, vindesine, cyclophosphamide, 5-FU and epirubicin in women with breast cancer; those with the highest levels of omega-3[docosapentaenoic acid, 22:5 (ω-3) and DHA] in breast adipose tissue were the most responsive to treatment. Prostate cancer In a joint Chinese-American study, a group of researchers from Wake Forest University School of Medicine in Winston-Salem, North Carolina, examined the influence of omega 3 and omega 6 on animal models of prostate cancer to assess whether a diet rich in omega-3 could reduce the incidence

4 of prostate cancer. The omega-3 rich diet reduced prostate tumor, slowed histopathological progression and increased survival. The effect of polyunsaturated fatty acids on prostate cancer development is mediated in part by the protein BAD, and induces apoptosis in prostate cancer cells. A study in 2009 showed how omega 3 fatty acids appear to protect against advanced prostate cancer, and this effect may be modified by a genetic variant in the cyclooxygenase 2 (COX-2) gene, a key enzyme in fatty acid metabolism and inflammation. The study found a protective relationship between omega-3 fatty acids consumption and prostate cancer. Researchers analyzed 466 men diagnosed with aggressive prostate cancer and 478 healthy controls. Diet was assessed with a food frequency questionnaire, and a genetic test in which nine COX-2 tag single nucleotide polymorphisms (SNP) were genotyped was performed. The researchers categorized intake of omega-3 fatty acids into quartiles based on the consumption distribution. The men whose dietary intake of long chain omega 3 fatty acids was the highest had a 64 percent less risk for aggressive prostate cancer compared to men whose intake was lowest. The authors then evaluated the effect of omega 3 fatty acids in men carrying a rs variant in COX-2, an inflammatory gene. Men who had a low omega 3 dietary intake and who carried this variant had a five times greater risk for aggressive prostate cancer, whereas those whose dietary intake of omega 3 was high had a much lower risk, even when they carried that COX-2 variant. The greater risk for the disease in the men carrying the COX-2 variant was reversed by increasing intake of omega 3 fatty acids by half a gram per day.

5 Colon cancer Long-chain omega-3 polyunsaturated fatty acids may have antineoplastic properties in the colon. Animal studies and some clinical trials suggest that fish oil supplements can reduce inflammation and have anticancer properties. A study of whites and African Americans showed that the risk of colon cancer was reduced by increasing intake of the two main fatty acids found in fish oil (EPA and DHA). In vitro studies on human cancer cells and in vivo studies in experimental animals have established the crucial role these fatty acids play in cancer etiology and are consistent with clinical trials that show a reduction of intestinal hyperproliferation following intake of omega-3 fatty acids in patients at high risk for colon cancer. At the Cancer Prevention Research Conference held by the American Association for Cancer Research, a group of scientists presented different data that revealed that omega-3 consumption may help prevent colorectal cancer. The effects obtained go from slowing tumor growth to the suppression and inhibition of metastasis (the process of forming new tumors).