Inhibition of colon cancer growth by docosahexaenoic acid involves autocrine production of TNFα

摘要: The omega-3 polyunsaturated fatty acid docosahexaenoic (DHA) has anti-inflammatory and anti-cancer properties. Among pro-inflammatory mediators, tumor necrosis factor α (TNFα) plays a paradoxical role in cancer biology with induction of cell death or survival depending on the cellular context. objective study was to evaluate TNFα DHA-mediated growth inhibition colon death. treatment human colorectal cells, HCT-116 HCT-8 DHA triggered apoptosis autocrine TNFα-dependent manner. We demonstrated that DHA-induced increased content mRNA occurred through post-transcriptional regulation via down-regulation microRNA-21 (miR-21) expression. Treatment led nuclear accumulation Foxo3a bounds miR-21 promoter triggering its transcriptional repression. Moreover, RIP1 kinase AMP-activated protein reduced nuclear-cytoplasmic shuttling subsequent increase expression decrease DHA-treated cells. Finally, we were able show xenograft tumor-bearing nude mice DHA-enriched diet induced an limiting cell-derived dependent Altogether, present work highlights novel mechanism for action involving mediated TNFα.