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Colon cancer is one of the most common malignancies in the western world and the second leading cause of cancer death in Korea. Epidemiology studies have shown a reduced incidence of colon cancer among populations consuming a large quantity of ω3-polyunsaturated fatty acids (ω3-PUFA) of ma- rine origin. Recently, it has been found that ω 3-PUFA has an antineoplastic effect in several cancers. This study was designed to investigate the mechanism of the anti-invasive effect of ω3-PUFA in colon cancer. ω3-PUFA, docosahexaenoic acids (DHA) and eicosapentaenoic acid ( EPA) treatment resulted in a dose-dependent inhibition of cell growth in SW480 human colon cancer cells. In contrast, arach- idonic acid (AA), a ω6-PUFA, exhibited no significant effect. This action likely involves apoptosis, giv- en that DHA treatment increased apoptotic cells in TUNEL assay. Moreover, invasiveness of SW480 cells was inhibited following treatment of DHA in a dose-dependent manner; in contrast, AA had no effect. The levels of MMP-9 and MMP-2 mRNA decreased after DHA pretreatment. MMP-9 and MMP-2 promoter activities were also inhibited by DHA treatment. The levels of NF-kB and p-IkB pro- tein were down-regulated by DHA pretreatment in a dose dependent manner. In addition, DHA in- hibited NF-kB promoter reporter activities. These findings suggest that ω3-PUFA may inhibit cancer cell invasion by inhibition of MMPs via reduction of NF-kB in colon cancer. In conclusion, ω3-PUFA could be used for chemoprevention and treatment of human colon cancer.

Mechanism of Anti-Invasive Action of Docosahexaenoic Acid in SW480 Human Colon Cancer Cell