Tumor growth suppression by -eleostearic acid, a linolenic acid isomer with a conjugated triene system, via lipid peroxidation

Abstract

We have previously shown that conjugated linolenic acids (CLnA) prepared by alkaline isomerization have a stronger antitumor effect than conjugated linoleic acids (CLA). In this study we have compared the suppressive effect on tumor growth of α-eleostearic acid (α-ESA, 9Z11E13E-18:3) with those of the CLA isomers 9Z11E-CLA and 10E12Z-CLA, using nude mice into which DLD-1 human colon cancer cells were transplanted. The results showed that α-ESA, which is a CLnA that can be prepared from natural sources in bulk, had a stronger antitumor effect than CLA. DNA fragmentation was enhanced and lipid peroxidation was increased in tumor tissues of the α-ESA-fed mice, which suggested that α-ESA induced apoptosis via lipid peroxidation. Furthermore, treatment of DLD-1 cells with α-ESA, 9Z11E-CLA and 10E12Z-CLA confirmed that α-ESA had a stronger antitumor effect than CLA in cultured cell lines. The induction of apoptosis by α-ESA was consistent with enhanced DNA fragmentation, increased caspase activity and increased expression of caspase mRNA following α-ESA treatment. Addition of α-tocopherol, an antioxidant, suppressed oxidative stress and apoptosis, suggesting that these effects were associated with lipid peroxidation.