Journal of Life Science (생명과학회지)

Korean Society of Life Science (한국생명과학회)
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Mechanism of Anti-Invasive Action of Docosahexaenoic Acid in SW480 Human Colon Cancer Cell

인체 대장암 세포주 SW480에서 docosahexaenoic acid에 의한 침윤억제 기전

  • Shin, So-Yeon (Department of Biochemisty, School of Medicine, Chungnam National University) ;
  • Kim, Yong-Jo (Department of Biochemisty, School of Medicine, Chungnam National University) ;
  • Song, Kyoung-Sub (Department of Biochemisty, School of Medicine, Chungnam National University) ;
  • Jing, Kaipeng (Department of Biochemisty, School of Medicine, Chungnam National University) ;
  • Kim, Na-Yeong (Department of Biochemisty, School of Medicine, Chungnam National University) ;
  • Jeong, So-Yeon (Department of Biochemisty, School of Medicine, Chungnam National University) ;
  • Park, Ji-Hoon (Department of Biochemisty, School of Medicine, Chungnam National University) ;
  • Seo, Kang-Sik (Department of Biochemisty, School of Medicine, Chungnam National University) ;
  • Heo, Jun-Young (Department of Biochemisty, School of Medicine, Chungnam National University) ;
  • Kwon, Hyun-Joo (Department of Biochemisty, School of Medicine, Chungnam National University) ;
  • Park, Jong-Il (Department of Biochemisty, School of Medicine, Chungnam National University) ;
  • Park, Seung-Kiel (Department of Biochemisty, School of Medicine, Chungnam National University) ;
  • Kweon, Gi-Ryang (Department of Biochemisty, School of Medicine, Chungnam National University) ;
  • Yoon, Wan-Hee (Department of Biochemisty, School of Medicine, Chungnam National University) ;
  • Hwang, Byung-Doo (Department of Biochemisty, School of Medicine, Chungnam National University) ;
  • Lim, Kyu (Department of Biochemisty, School of Medicine, Chungnam National University)
  • 신소연 (충남대학교 의학전문대학원 생화학교실) ;
  • 김용조 (충남대학교 의학전문대학원 생화학교실) ;
  • 송경섭 (충남대학교 의학전문대학원 생화학교실) ;
  • ;
  • 김나영 (충남대학교 의학전문대학원 생화학교실) ;
  • 정소연 (충남대학교 의학전문대학원 생화학교실) ;
  • 박지훈 (충남대학교 의학전문대학원 생화학교실) ;
  • 서강식 (충남대학교 의학전문대학원 생화학교실) ;
  • 허준영 (충남대학교 의학전문대학원 생화학교실) ;
  • 권현주 (충남대학교 의학전문대학원 생화학교실) ;
  • 박종일 (충남대학교 의학전문대학원 생화학교실) ;
  • 박승길 (충남대학교 의학전문대학원 생화학교실) ;
  • 권기량 (충남대학교 의학전문대학원 생화학교실) ;
  • 윤완희 (충남대학교 의학전문대학원 생화학교실) ;
  • 황병두 (충남대학교 의학전문대학원 생화학교실) ;
  • 임규 (충남대학교 의학전문대학원 생화학교실)
  • Received : 2010.01.25
  • Accepted : 2010.02.20
  • Published : 2010.04.30
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Abstract

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 ${\omega}3$-polyunsaturated fatty acids (${\omega}3$-PUFA) of marine origin. Recently, it has been found that ${\omega}3$-PUFA has an antineoplastic effect in several cancers. This study was designed to investigate the mechanism of the anti-invasive effect of ${\omega}3$-PUFA in colon cancer. ${\omega}3$-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 ${\omega}6$-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 ${\omega}3$-PUFA may inhibit cancer cell invasion by inhibition of MMPs via reduction of NF-kB in colon cancer. In conclusion, ${\omega}3$-PUFA could be used for chemoprevention and treatment of human colon cancer.

대장암은 미국 등 서양 국가뿐만 아니라 국내에서도 2번째로 많이 발병이 되는 암으로 알려져 있다. 역학조사에 의하면 ${\omega}3$-PUFAs를 많이 섭취한 인종에서 대장암 발생빈도가 감소하고 최근 ${\omega}3$-PUFAs는 수종의 암에 대해 항암작용을 나타낸다고 한다. 이에 본 연구에서는 대장암에서 DHA 등 ${\omega}3$-PUFA의 항침윤 기전을 규명하여 다음과 같은 결과를 얻었다. DHA및 EPA는 대장암 세포주 SW480의 증식을 농도 의존적으로 억제하였으나 AA는 거의 영향이 없었으며 TUNEL assay로 apoptotic cell death가 확인 되었다. DHA는 $\beta$-catenin 단백 및 TCF/LEF luciferase 활성을 농도 의존적으로 억제 하였다. SW480 세포의 침윤능은 DHA의 농도에 의존적으로 억제되었다. DHA처리 후 MMP-9 및 MMP-2 mRNA양이 감소되었을 뿐만 아니라 그 promoter의 reporter 활성도 억제되었다. NF-kB 및 p-IkB 단백질양도 DHA의 처리농도에 의존적으로 감소하였으며 NF-kB promoter의 활성도 억제되었다. 이상의 결과로 ${\omega}3$-PUFA는 대장암에서 NF-kB 신호전달 차단에 의한 MMP-2 및 MMP-9 발현을 억제하여 침윤을 억제하여 항암작용을 나타낼 수 있음을 시사하며, 따라서 ${\omega}3$-PUFA는 대장암의 예방 및 치료에 유용하게 사용될 수 있으리라 생각된다.

Keywords

References

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