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Effect of Eupatorium japonicum Extract on the Metastasis, Invasion and Adhesion of MDA-MB-231 Human Breast Cancer Cells

등골나물 추출물이 인간의 유방암세포인 MDA-MB-231 세포의 이동, 침윤 및 부착에 미치는 영향

  • Woo, Eun-Young (Department of Food Science and Nutrition, Hallym University) ;
  • Park, So-Young (Department of Food Science and Nutrition, Hallym University) ;
  • Kwon, Soo-Jin (Department of Food Science and Nutrition, Hallym University) ;
  • Kwon, Gyoo-Taik (Department of Food Science and Nutrition, Hallym University) ;
  • Kim, Jong-Dae (Department of Food Science and Biotechnology, Kangwon National University) ;
  • Lim, Soon-Sung (Department of Food Science and Nutrition, Hallym University) ;
  • Yoon, Jung-Han (Department of Food Science and Nutrition, Hallym University)
  • 우은영 (한림대학교 식품영양학과) ;
  • 박소영 (한림대학교 식품영양학과) ;
  • 권수진 (한림대학교 식품영양학과) ;
  • 권규택 (한림대학교 식품영양학과) ;
  • 김종대 (강원대학교 바이오산업공학부 식품생명공학) ;
  • 임순성 (한림대학교 식품영양학과) ;
  • 윤정한 (한림대학교 식품영양학과)
  • Received : 2010.10.30
  • Accepted : 2010.12.09
  • Published : 2011.04.30

Abstract

The metastatic effect of Eupatorium japonicum extract (EJE) on MDA-MB-231 human breast cancer cells was investigated. MDA-MB-231 cells were treated with various concentrations of EJE (0, 5, 10 and $20{\mu}g/mL$). EJE inhibited cell migration, invasion and adhesion of MDA-MB-231 cells in dose-dependent manners. Gelatin zymography exhibited that EJE significantly down regulated secretion of matrix metalloproteinase (MMP)-9 and MMP-2. EJE decreased the protein levels of tissue inhibitor of metalloproteinase (TIMP)-1 but increased TIMP-2 levels. Additionally, EJE reduced the protein and mRNA levels of urokinase-type plasminogen activator (uPA), vascular endothelial growth factor (VEGF) and intercellular adhesion molecule (ICAM). In several solvent fractions of EJE, the hexane fraction markedly decreased MDAMB-231 cell migration. Thus, these finding suggest that EJE may be a potential antimetastatic agent, which can considerably inhibit the metastatic and invasive capacity of breast cancer cells.

등골나물은 국화과 여러해살이 식물로 한방에서는 고혈압, 폐렴, 황달, 홍역, 요통 등에 사용한다고 알려져 있다. 본 연구에서는 등골나물의 꽃 부위를 추출하여 등골나물 추출물이 유방암 세포인 MDA-MB-231 세포의 이동, 침윤 및 부착에 미치는 영향을 조사하였다. 그 결과 MDA-MB-231 세포의 이동, 침윤 및 부착은 등골나물 추출물의 농도($0-20{\mu}g/mL$)가 증가할수록 현저하게 감소하였다. 등골나물 추출물은 MMP-9, MMP-2의 활성을 억제하였고, TIMP-1의 발현은 감소시킨 반면 TIMP-2의 발현은 증가시켰다. 또한, 등골나물 추출물은 uPA, VEGF 그리고 ICAM의 mRNA 및 단백질 수준을 현저히 감소시켰다. 특히, 등골나물 헥산 분획물이 유방암세포의 이동을 현저하게 억제하였다. 이상의 결과로부터 등골나물 추출물은 MMP-9, MMP-2, uPA, TIMP-1 및 ICAM의 감소, TIPM-2의 증가를 통해 유방암세포의 전이를 억제하는 것으로 판단된다. 따라서 본 연구는 이러한 효능을 지닌 등골나물 추출물을 암전이에 효과가 있는 암예방제나 항암제로 개발할 수 있는 가능성을 제시한다.

Keywords

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