Selective increase in the sensitivity of tumours to chemotherapy with n-3 polyunsaturated fatty acids

Since long chain polyunsaturated fatty acids (PUFA) are good substrate for peroxydation, a biochemical correlate of cancer cell programmed death and s ince some cytotoxic agents such as anthracyclins are known to induce oxidat ive stress, we looked for the effect of PUFA on the response of the cancer disease to anthracyclins-based chemotherapy. We found that breast cancer pa tients with elevated DHA content in while adipose tissues taken as an indic ator of post dietary intake had a better response rate to anthracyclines-co ntaining neoadjuvant chemotherapy than patients with low DHA level, suggest ing that chemosensitivity of the carcinoma was higher when DHA availability to the tumor tissue was greater: Such a hypothesis was examined using huma n breast carcinoma cell cultures. Long chain PUFA and especially docosahexa enoic acid (22:6n-3) increased the sensitivity of breast cancer cell lines to anthracyclins. Using the rat model of NMU-induced mammary tumors, we doc umented an increased efficacy of anthracyclins on mammary tumors without ch ange in cardiac toxicity in the dietary group supplemented with fish oil, e nriched in n-3PUFAs, or with purified DHA. This shows that this fatty acid also sensitizes the tumor in vivo. A clinical trial investigating the poten tial of dietary DHA to increase the response rate of measurable metastatic tumors in breast cancer patients will be conducted shortly.