Evidence for potential mechanisms for the effect of conjugated linoleic acid on tumor metabolism and immune function: lessons from n-3 fatty acids.

Conjugated linoleic acid (CLA) and the long-chain polyunsaturated n-3 fatty acids have been shown in vivo and in vitro to reduce tumor growth. Tumor growth could occur by slowing or stopping cell replication (by interfering with transition through the cell cycle), increasing cell death (via necrosis and/or apoptosis), or both. The anticancer effects of fatty acids, shown in vivo, could also be mediated by effects on the host's immune system. Although it is widely recognized that n-3 fatty acids can alter immune and inflammatory responses, considerably less is known about CLA. For n-3 fatty acids, several candidate mechanisms have been proposed for their immune effects, including changes in 1) membrane structure and composition, 2) membrane-mediated functions and signals (eg, proteins, eicosanoids), 3) gene expression, and 4) immune development. Considerable work has been done that shows the potential importance of CLA as an anticancer treatment; however, many questions remain as to how this effect occurs. This review summarizes the CLA and cancer literature and then uses the evidence for the anticancer immune and tumor properties of the long-chain n-3 fatty acids docosahexaenoic and eicosapentaenoic acids to suggest future research directions for mechanistic studies on CLA and cancer.