Conjugated eicosapentaenoic acid (CEPA) and conjugated docosahexaenoic acid (CDHA) with triene structure, isomerized by alkaline treatment, showed intensive cytotoxicity with LD50 at 12 and 16 mu M, respectively, in DLD-1 cells (colorectal adenocarcinoma), while they had no effect on normal human fibroblast cell lines such as MRC-5, TIG-103, and KMS-6 cells, Cytotoxic action of CEPA and CDHA was also demonstrated in other tumor cell lines including HepG2, A549, MCF-7, and MKN-7 cells. cu-Tocopherol suppressed cytotoxicity of CEPA and CDHA in tumor cells, and the cytotoxicity involved membrane phospholipid peroxidation. CEPA and CDHA induced DNA condensation and fragmentation in DLD-1 cells, indicating the involvement of apoptosis in this cytotoxic mechanism. Furthermore, previous reports have shown that lipid peroxidation product induces cell death, including apoptotic cell death in different cell lines. CEPA and CDHA have been demonstrated in cultured cells to cause cell death via lipid peroxidation and apoptosis in the absence of cu-tocopherol.