Augmentation sélective de la sensibilité des tumeurs à la chimiothérapie par les acides gras polyinsaturés n-3

Abstract

Since long chain polyunsaturated fatty acids (PUFA) are good substrate for peroxydation, a biochemical correlate of cancer cell programmed death and since some cytotoxic agents such as anthracyclins are known to induce oxidative stress, we looked for the effect of PUFA on the response of the cancer disease to anthracyclins-based chemotherapy. We found that breast cancer patients with elevated DHA content in white adipose tissues taken as an indicator of post dietary intake had a better response rate to anthracyclines-containing neoadjuvant chemotherapy than patients with low DHA level, suggesting that chemosensitivity of the carcinoma was higher when DHA availability to the tumor tissue was greater. Such a hypothesis was examined using human breast carcinoma cell cultures. Long chain PUFA and especially docosahexaenoic acid (22:6n-3) increased the sensitivity of breast cancer cell lines to anthracyclins. Using the rat model of NMU-induced mammary tumors, we documented an increased efficacy of anthracyclins on mammary tumors without change in cardiac toxicity in the dietary group supplemented with fish oil, enriched in n-3PUFAs, or with purified DHA. This shows that this fatty acid also sensitizes the tumor in vivo. A clinical trial investigating the potential of dietary DHA to increase the response rate of measurable metastatic tumors in breast cancer patients will be conducted shortly.