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Cordycepin Inhibits Migration and Invasion of HCT116 Human Colorectal Carcinoma Cells by Tightening of Tight Junctions and Inhibition of Matrix Metalloproteinase Activity

Cordycepin의 치밀결합 강화 및 MMPs의 활성 억제를 통한 HCT116 인체대장암세포의 이동성 및 침윤성의 억제

  • Jeong, Jin Woo (Center for Core Research Facilities, Daegu Gyeongbuk Institute of Science & Technology) ;
  • Choi, Yung Hyun (Dept. of Biochemistry, Dongeui University College of Oriental Medicine, Anti-Aging Research Center & Blue-Bio Industry RIC, Dongeui University)
  • 정진우 (대구경북과학기술원 중앙기기센터) ;
  • 최영현 (동의대학교 한의과대학 생화학교실 및 항노화연구소 및 블루바이오소재개발센터)
  • Received : 2013.09.10
  • Accepted : 2013.10.30
  • Published : 2014.01.31

Abstract

Cordycepin is the major functional component of Cordyceps species and is widely used in traditional oriental medicine. Cordycepin has been shown to possess many pharmacological properties, such as enhancement of immune function along with anti-inflammatory, antioxidant, anti-aging, and anti-cancer effects. Here, we investigated the inhibitory effects of cordycepin on cell migration and invasion, which are two critical cellular processes that are often deregulated during metastasis, using HCT116 human colorectal carcinoma cells. According to our data, cordycepin at non-cytotoxic concentrations markedly inhibited the motility and invasiveness of HCT116 cells in a time-dependent manner. RT-PCR and Western blotting results indicated that cordycepin reduced the levels of claudin proteins, which are major components of tight junctions (TJs), and induced tightening of TJs. Cordycepin also attenuated the expression and activities of matrix metalloproteinases (MMPs)-2 and -9, whereas levels of tissue inhibitor of metalloproteinases (TIMPs)-1 and -2 were simultaneously elevated. These findings suggest that cordycepin reduces the migration and invasion of HCT116 cells by modulating the activities of TJs and MMPs.

Cordycepin은 C. militaris의 주요 생리활성 물질로서 인체 면역기능 강화, 항염증, 항산화, 항노화 및 항암활성을 포함한 다양한 약리효능이 있는 것으로 알려져 있다. 본 연구에서는 HCT116 대장암세포를 이용하여 암전이의 주요 과정인 암세포의 이동성 및 침윤성에 미치는 cordycepin의 효능에 관하여 조사하였다. 본 연구의 결과에 의하면 세포독성이 없는 범위에서 cordycepin은 HCT116 세포의 이동성과 침윤성을 유의적으로 억제하였다. RT-PCR 및 Western blotting 결과에 의하면 cordycepin은 TJs의 주요 구성인자인 claudin family 인자들의 발현을 억제하였으며, 이는 TJ의 전기적 저항성의 증대와 연관이 있었다. Cordycepin은 또한 MMP-2 및 -9의 발현과 활성을 저해함과 동시에 TIMP-1 및 -2의 발현은 증가시켰다. 따라서 cordycepin에 의한 HCT116 대장암세포의 전이능 억제는 TJ의 견고성 증대와 MMPs의 활성 억제와 연관성이 있음을 알 수 있었다.

Keywords

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