title: Synthesis of the conjugated trienes 5E,7E,9E,14Z,17Z-eicosapentaenoic acid and 5Z,7E,9E,14Z,17Z-eicosapentaenoic acid, and their induction of apoptosis in DLD-1 colorectal adenocarcinoma cells.
abstract: During the course of our recent study on the anti-tumor effect of conjugated eicosapentaenoic acids (CEPA), we found that acid mixtures prepared by treating EPA with KOH in ethylene glycol induced potent apoptotic cell death in human tumor cells via membrane phospholipid peroxidation. Interestingly, the KOH-treated CEPA mixtures were more cytotoxic than EPA and CLA and had no effect on normal human fibroblast cells. To identify the specific cytotoxic FA in the CEPA mixture, we synthesized possible candidates for the active species. Here, we report the synthesis of (5E,7E,9E, 14Z, 17Z)-5,7,9,14,1 7-eicosapentaenoic acid (E-CEPA) and its 5-(Z) isomer (Z-CEPA), both of which are conjugated trienes that exist naturally in red algae (Ptilota filicina J. Agardh). E-CEPA and Z-CEPA were synthesized from methyl 5-oxopentanoate in six steps, using three types of Wittig reactions as the key steps. Next, we examined the cytotoxicity of E-CEPA and Z-CEPA in human tumor cells and confirmed their bioactivity. Both E-CEPA and Z-CEPA had a strong cytotoxic reaction in tumor cells, and this effect occurred through induction of apoptosis.
authors.affiliation: Food & Biodynamic Chemistry Laboratory, Graduate School of Agricultural Science, Tohoku University, Sendai 981-8555, Japan.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Tsuzuki
authors.forename: Kazumi
authors.initials: K
authors.lastname: Tanaka
authors.forename: Shigefumi
authors.initials: S
authors.lastname: Kuwahara
authors.forename: Teruo
authors.initials: T
authors.lastname: Miyazawa
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D004354:Drug Screening Assays, Antitumor; D015118:Eicosapentaenoic Acid / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D013237:Stereoisomerism
chemical_list: D000970:Antineoplastic Agents; C052214:5,7,9,14,17-eicosapentaenoic acid; D015118:Eicosapentaenoic Acid