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KMID : 0613820100200040561
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Journal of Life Science
2010 Volume.20 No. 4 p.561 ~ p.571
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Mechanism of Anti-Invasive Action of Docosahexaenoic Acid in SW480 Human Colon Cancer Cell
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Shin So-Yeon
Kim Yong-Jo
Song Kyoung-Sub
Kaipeng Jing
Kim Na-Yeong
Jeong So-Yeon
Park Ji-Hoon
Seo Kang-Sik
Heo Jun-Young
Kwon Hyun-Joo
Park Jong-Il
Park Seung-Gil
Kwon Gi-Ryang
Yun Wan-Hee
Hwang Byung-Doo
Im Kyu
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Abstract
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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 marine origin. Recently, it has been found that ω3-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, arachidonic acid (AA), a ω6-PUFA, exhibited no significant effect. This action likely involves apoptosis, given 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 protein were down-regulated by DHA pretreatment in a dose dependent manner. In addition, DHA inhibited 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.
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KEYWORD
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SW480, DHA, MMP-2, MMP-9, NF-kB
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