Colon cancer therapy: new perspectives of nutritional manipulations using polyunsaturated fatty acids

Recent advances in the development of new therapeutic strategies combining conventional adjuvant radio/chemotherapy with nutritional manipulations with n-3 polyunsaturated fatty acids (PUFAs) are presented.

Studies in cell culture and tumour-bearing animals have reported the ability of long-chain n-3 PUFAs to enhance the cytotoxicity of several anticancer drugs. In colon cancer, combination of n-3 PUFAs with 5-fluorouracil resulted in an additive growth inhibitory effect on different cell lines. Moreover, recent findings suggest that eicosapentaenoic or docosahexaenoic acid may be used to enhance tumour radiosensitivity while reducing mucosal/epidermal radiotoxicity similar to radioprotective agents. The underlying mechanism is probably mediated through lipid peroxidation because the antitumour effect of n-3 PUFAs is shared with the n-6 PUFA, arachidonic acid, and abolished by vitamin E. In vivo, the use of n-3 PUFAs may provide an additional advantage compared with n-6 PUFAs. Downregulation of eicosanoid synthesis from cyclooxygenase II may reduce angiogenesis, inflammation and metastasis induction.

New insights suggest that n-3 PUFAs may play an important role not only in cancer prevention but also in cancer management. They may act synergistically with radio/chemotherapy to kill tumour cells by increasing oxidative stress while reducing angiogenesis, inflammation and metastasis induction.