Omega-3 polyunsaturated fatty acids and cancer: lessons learned from clinical trials

Over the past decades, extensive studies have addressed the therapeutic effects of omega-3 polyunsaturated fatty acids (omega-3 FAs) against different human diseases such as cardiovascular and neurodegenerative diseases, cancer, etc. A growing body of scientific research shows the pharmacokinetic information and safety of these natural occurring substances. Moreover, during recent years, a plethora of studies has demonstrated that omega-3 FAs possess therapeutic role against certain types of cancer. It is also known that omega-3 FAs can improve efficacy and tolerability of chemotherapy. Previous reports showed that suppression of nuclear factor-κB, activation of AMPK/SIRT1, modulation of cyclooxygenase (COX) activity, and up-regulation of novel anti-inflammatory lipid mediators such as protectins, maresins, and resolvins, are the main mechanisms of antineoplastic effect of omega-3 FAs. In this review, we have collected the available clinical data on the therapeutic role of omega-3 FAs against breast cancer, colorectal cancer, leukemia, gastric cancer, pancreatic cancer, esophageal cancer, prostate cancer, lung cancer, head and neck cancer, as well as cancer cachexia. We also discussed the chemistry, dietary source, and bioavailability of omega-3 FAs, and the potential molecular mechanisms of anticancer and adverse effects.