Inhibitory effect of n3 polyunsaturated fatty acids on cancer cell growth by p53 activation

Abstract

Different evidences show the regulatory effect of n-3 and n-6 polyunsaturated fatty acids (PUFAs) on carcinogenesis, however how PUFAS modulate tumor development remains unknown. In this report, we analyzed the in vitro and in vivo effects of n-3 and n-6 PUFAs on a syngeneic murine mammary adenocarcinoma cell line (LMM3). Tumor cells viability was measured by Resazurin and apoptosis by Hoechst. The PUFAs tumor cell membrane profile was analyzed by Gas Chromatography and PUFAs derivatives (eicosanoids) by HPLC. Our results showed that alpha linolenic acid (ALA, C 18:3 n-3) induced significantly higher pro-apoptotic effects than linoleic acid (LA, C18: 2, n-6). Moreover, ex-vivo studies showed that tumor cells from mice fed with ALA enriched diet diminished tumorigenesis by decreasing the tumor cell release of 12 (S)-HETE, a pro-carcinogenic eicosanoid and producing higher levels of pro-apoptotic 12(S)-HHT. In addition, the ALA enriched diet resulted on a higher tumor tissue expression of the pro-apoptotic tp53 tumor suppressor factor. These results provide evidence of the biological pro-apoptotic effects of n-3 PUFAs and particularly, the fatty acid ALA, as the regulator of the signaling pathway tp53. This provided a novel mechanism and a potential target on anticancer treatment.