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β-Sitosterol에 의한 인체 대장암 HCT116 세포의 증식억제에 관한 연구

β-Sitosterol Induced Growth Inhibition is Associated with Up-regulation of Cdk Inhibitor p21WAF1/CIP1 in Human Colon Cancer Cells

  • 최영현 (동의대학교 한의과대학 생화학교실) ;
  • 김영애 (부산대학교 생활과학대학 식품영양학과) ;
  • 박철 (부산대학교 자연과학대학 생물학과) ;
  • 최병태 (동의대학교 한의과대학 해부학교실) ;
  • 이원호 (부산대학교 자연과학대학 생물학과) ;
  • 황경미 (부산대학교 생활과학대학 식품영양학과) ;
  • 정근옥 (부산대학교 생활과학대학 식품영양학과) ;
  • 박건영 (부산대학교 생활과학대학 식품영양학과)
  • Choi, Yung-Hyun (Dept. of Biochemistry, College of Oriental Medicine, Dongeui University) ;
  • Kim, Young-Ae (Dept. of Food Science and Nutrition, Pusan National University) ;
  • Park, Cheol (Dept. of Biology, Pusan National University) ;
  • Choi, Byung-Tae (Dept. of Anatomy, College of Oriental Medicine, Dongeui University) ;
  • Lee, Won-Ho (Dept. of Biology, Pusan National University) ;
  • Hwang, Kyung-Mi (Dept. of Food Science and Nutrition, Pusan National University) ;
  • Jung, Keun-Ok (Dept. of Food Science and Nutrition, Pusan National University) ;
  • Park, Kun-Young (Dept. of Food Science and Nutrition, Pusan National University)
  • 발행 : 2004.01.01

초록

$\beta$-Sitosterol은 과일과 야채 등을 포함한 대부분의 고등식물에 존재하는 중요한 phytosterol의 하나로서, 인체 암의 예방과 치료에 매우 유효한 것으로 보고되어져 오고 있다. 본 연구에서는 $\beta$-sitosterol의 암세포 증식억제 기전의 해석을 시도하기 위하여 인체 대장암세포 HCT116의 증식에 미치는 $\beta$-sitosterol의 영향을 조사하였다. $\beta$-Sitosterol의 처리로 HCT116 암세포의 증식은 처리 농도 의존적으로 감소되었으며, 특히 7.5 $\mu$M 이상 처리에서는 급격한 성장억제 효과가 있었다. 또한 5.0 $\mu$M 처리군에서부터 apoptotic body의 형성이 관찰되었고, $\beta$-catenin 단백질의 분해 현상과 연관성이 있었다. 그리고 $\beta$-sitosterol이 처리된 암세포에서는 종양억제유전자 p53 및 Cdk inhibitor p21의 발현이 전사 및 번역 수준에서 모두 증가되었다. 본 결과는 그동안 연구가 거의 진행되어져 있지 않았던 $\beta$-sitosterol에 의한 암세포주기 조절 해석을 위한 주요한 자료로 활용될 것이다.

$\beta$-Sitosterol is the major phytosterol in higher plants, including fruits and vegetables. The molecule has been shown to have the potential for prevention and therapy for human cancer. We investigated the effects of $\beta$-sitosterol on the cell proliferation of HCT116 human colon cancer cells in order to understand its anti-proliferative mechanism. $\beta$-Sitosterol treatment resulted in the inhibition of cell proliferation in a concentration-dependent manner. The anti-proliferative effect of HCT116 cells by $\beta$-sitosterol was associated with formation of apoptotic bodies and degradation of $\beta$-catenin protein. In addition, $\beta$-sitosterol-treatment induced a marked accumulation of tumor suppressor p53 and a concomitant induction of cyclin-dependent kinase (Cdk) inhibitor p21 without alteration in the levels of cyclins and Cdks. Taken together, these findings provide important new insights into the possible molecular mechanisms of the anti-cancer activity of $\beta$-sitosterol.

키워드

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  2. Anti-Cancer Effects of Oldenlandia diffusa extract on WiDr human colorectal adenocarcinoma cells vol.23, pp.1, 2015, https://doi.org/10.14374/HFS.2015.23.1.101
  3. 식중독유발 세균의 증식에 미치는 백화사설초 추출물의 영향 vol.34, pp.1, 2004, https://doi.org/10.3746/jkfn.2005.34.1.107