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Inhibitory Effect of the Methanolic Extract of Symphyocladia latiuscula on the Growth of HT-29 Human Colon Cancer Cells

보라우무 메탄올추출물의 HT-29 대장암세포 증식 억제 효과

  • Kim, Eun-Ji (Center for Efficacy Assessment and Development of Functional Foods and Drugs Hallym University) ;
  • Park, So-Young (Dept. of Food Sciences and Nutrition, Hallym University) ;
  • Hong, Ji-Eun (Dept. of Food Sciences and Nutrition, Hallym University) ;
  • Shin, Min-Jeong (Dept. of Food Sciences and Nutrition, Hallym University) ;
  • Lim, Soon-Sung (Center for Efficacy Assessment and Development of Functional Foods and Drugs Hallym University) ;
  • Shin, Hyun-Kyung (Center for Efficacy Assessment and Development of Functional Foods and Drugs Hallym University) ;
  • YoonPark, Jung-Han (Center for Efficacy Assessment and Development of Functional Foods and Drugs Hallym University)
  • 김은지 (한림대학교 식의약품의 효능평가 및 기능성소재개발센터) ;
  • 박소영 (한림대학교 식품영양학과) ;
  • 홍지은 (한림대학교 식품영양학과) ;
  • 신민정 (한림대학교 식품영양학과) ;
  • 임순성 (한림대학교 식의약품의 효능평가 및 기능성소재개발센터) ;
  • 신현경 (한림대학교 식의약품의 효능평가 및 기능성소재개발센터) ;
  • 윤정한 (한림대학교 식의약품의 효능평가 및 기능성소재개발센터)
  • Published : 2007.04.30

Abstract

In the present study, twenty eight marine algae species were evaluated for their antiproliferative effect on HT-29 human colon cancer cells. Among these, the methanolic extract of Symphyocladia latiuscula (SL Ex) showed the highest inhibitory activity on HT-29 cell growth. In this study, we examined the mechanism by which SL Ex inhibited the HT-29 cell growth. Cells were cultured with various concentrations of $(0{\sim}20{\mu}g/mL)$ SL Ex. The SL Ex substantially decreased the viable cell numbers and induced apoptosis of HT-29 cells in a dose-dependent manner Western blot analyses of total cell lysates revealed that SL Ex increased the levels of cleaved caspase-8, -9, -7, and -3, and poly (ADP-ribose) polymerase in HT-29 cells. In addition, SL Ex increased truncated Bid levels but moderately decreased Bax levels at only $20{\mu}g/mL$. Furthermore, SL Ex did not affect Bcl-2 protein levels but increased the levels of Fas in HT-29 cells. The present results indicate that SL Ex inhibits cell growth via inducing apoptosis in human colon cancer cells. The mechanism of apoptosis induction by SL Ex involves caspase-8 activation leading to changes in mitochondrial events and subsequent activation of the caspase-7/caspase-3 cascade. Our finding may lead to the development of new therapeutic strategies for the treatment of colon cancer.

해조류는 다양한 생리 활성을 나타내는 성분들을 함유하고 있어 항산화효과 등 다양한 생리활성 효과를 나타내는 것으로 보고되고 있다. 본 연구에서는 식용 가능한 28종의 해조류 메탄올추출물 중 보라우무 메탄올추출물이 인간의 대장에서 유래한 암세포인 HT-29세포의 세포증식을 억제함을 밝혔고, 가장 강한 HT-29 세포 증식 억제 효과를 나타낸 보라우무 메탄올추출물의 대장암세포 증식억제 기전을 밝히고자 하였다. 보라우무 메탄올추출물을 HT-29 세포 배양액에 여러 농도$(0{\sim}20{\mu}g/mL)$로 첨가하여 세포를 배양한 경우 보라우무 메탄올추출물 처리 농도가 증가할수록 세포증식이 현저히 감소하였고, apoptotic cell수는 현저히 증가하였다. Apoptosis의 주요한 조절인자인 Bcl-2 family 단백질 중 Bcl-2는 보라우무 메탄올추출물에 의해 변화가 없었고 Bax는 고농도에서만 소폭 감소하였다. 반면, t-Bid 단백질 수준은 보라우무 메탄올추출물의 처리에 의해 현저하게 증가하였다 Bcl-2 family Protein과 더불어 apoptosis의 조절에 주요한 역할을 하는 caspase 단백질의 경우 보라우무메탄올추출물 처리에 의해 cleaved caspase-8, -9, -7, -3 단백질 수준이 현저히 증가하였고, cleaved PARP 단백질수준도 현저히 증가하였다. 또한, caspase-8의 활성화를 유도하는 Fas 단백질 수준도 보라우무 메탄올추출물에 의해 현저하게 증가하였다. 이 결과로부터 보라우무 메탄올추출물은 caspase-8의 활성 증가에 의한 미토콘드리아 막 투과성 변화와 caspase-7/-3 활성의 증가를 통해 apoptosis를 유도함으로써 암세포의 증식을 억제한다는 결론을 내릴 수 있다. 본 연구는 보라우무를 항암효과를 지니는 기능성식품이나 항암제로 개발할 수 있는 가능성을 제시하고 있으며 향후 보라우무를 이용한 제품의 개발을 위해서는 유효성분의 동정 및 그 성분의 작용 기전에 대한 면밀한 추가 연구가 필요할 것으로 보인다.

Keywords

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