Therapeutic Effects of Omega-3 Fatty Acids in Colon Cancer Patients

Abstract

Incidence of colorectal cancer is increasing in worldwide with economic development. The causes of colorectal cancer are associated with the lack of physical activity, obesity, excessive intake of fat and meat, and lack of ietary fiber intake. Epidemiological studies suggested that there is an inverse correlation between consumption of fish and cancer risk and positive correlation between consumption of meat and meat products and colon cancer incidence. Both the type and amount of dietary fats consumed have been implicated in colon cancer etiology. A diet rich in saturated fatty acids have been known as an established risk factor for the onset of colon cancer. Whereas, omega 3 (n-3) fatty acids has been known to lower the incidence of this malignancy. A large number of studies have shown that fat composition has the potential to prevent and treat cancer. Increased ratio of omega 6 (n-6) to n-3 fatty acid contributes to the colon carcinogenesis. The level of n-6 fatty acids in the Western diet is more than 40 times higher than those in n-6 fatty acids. Therefore, the Western style diet has been known to be implicated in colon carcinogenesis, tumor growth, invasion and metastasis of colon cancer. n-3 fatty acids and their metabolites exert anti-carcinogenic activities in various cancer models by influencing the gene expression or activation of signal transduction molecules involved in the control of cell proliferation, differentiation apoptosis, angiogenesis, and metastasis. In addition, oral administration of n-3 fatty acids has shown that the inhibition of tumor growth and apoptosis in the various types of cancers, including lung, colon, pancreatic, esophageal, liver, breast, prostate, brain. Especially, docosahexaenoic acid (DHA) present in fish oil reduces expression of cyclin D1, cyclin E, cyclin A- associate kinases, which lead to cell cycle arrest in colon cancer cells. DHA-mediated stimulation of TRAIL(tumor necrosis factor-related apoptosis inducing ligand)-induced apoptosis was associated with extensive engagement of mitochondrial pathway (Bax/Bak activation, drop of mitochondrial membrane potential, cytochrome c release), activation of endoplasmic reticulum stress response, decrease of anti-apoptotic protein (XIAP,cIAP1) levels and significant changes in sphingolipid metabolism. In addition, DHA down-regulated the several other proteins regulated by the TCF-beta-catenin pathway and peroxisome proliferator-activated receptor-delta, membrane type 1(MT1)-matrix metalloproteinase (MMP), MMP-7 and vascular endothelial growth factor. Moreover, dietary intake of n-3 fatty acids improves efficacy of chemotherapeutic agents in the clinical and preclinical studies through suppression of inflammation. N-3 supplement decreased the level of inflammatory markers (tumor necrosis factor-α, interleukin-1β,soluble interleukin-2 receptor, interleukin-6, and interleukin-8 in the serum of colon cancer patients. N-3 fatty acids sensitize the cancer cells to chemotherapeutic agents in colon cancer patients. Also fish oil improves numbers and function of neutrophil in cancer surgery patients undergoing chemotherapy. In addition, n-3 fatty acids reduced the side effects of chemotherapeutic agents. Moreover, n-3 fatty acids improve the cachexia in the colon cancer patients. Cancer patients who consumed n-3 fatty acids as a supplement showed the weight gain and increase the lean body mass (LBM) than the individuals without n-3 fatty acids, which is associated with enhancement of plasma eicosapentanoic acid (EPA) levels. Cancer patients who consumed n-3 fatty acids as a supplement showed weight gain, increased LBM and fat mass, high opportunity of physical activity, enhancement of life quality, survival period, and immune function. Taken together above findings, n-3 fatty acid, especially, EPA and DHA have potent anti-inflammatory, anti-apoptosis, anti-proliferative,anti-angiogenesis, anti-invasion, and anti-metastatic effects. N-3 fatty acids as a supplementation offer the variable health benefits at a biochemical, clinical, and functional level in the colon cancer patients. The recommended intake of DHA and EPA set by the American Heart Association is 0.5 g/day EPA+DHA for those without heart disease, 0.8- 1.8 g/day of EPA+DHA for those with heart disease, and no more than 3 g/day EPA+DHA unless under the supervision of a physician, due to increased risk of bleeding. In the most clinical trials, colorectal cancer patients received nutritional supplement providing 1 ~ 2 g of n- 3 fatty acids per day. Intake of omega 3 fatty acid as an adjuvant is a supportive therapy to decelerate cancer progression and to enhance the cancer therapy and to prevent relapse. However, future investigations on the beneficial/risk effects of n-3 and n-6 fatty acids in colon cancer prevention/treatment are required to find reliable and best way to use these n-3 fatty acids for colon cancer patients.