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인체 유방암세포에서 TPA에 의해 유도된 matrix metalloproteinases 활성 및 침윤성 증대에 미치는 genistein의 영향

Genistein Suppresses TPA-Induced Matrix Metalloproteinases Activity and Cell Invasion in Human Breast Adenocarcinoma Cells

  • 최영현 (동의대학교 한의과대학 생화학교실, 대학원 바이오물질제어학과, 항노화연구소 및 블루바이오소재개발센터) ;
  • 김성옥 (대구한의대학교 본초약리학교실 및 BK21 한방신약개발연구팀)
  • Choi, Yung-Hyun (Department of Biochemistry, College of Oriental Medicine, Department of Biomaterial Control (BK21 program), Anti-Aging Research Center & Blue-Bio Industry RIC, Dongeui University) ;
  • Kim, Sung-Ok (Department of Herbal Pharmacology of Oriental Medicine, College of Oriental Medicine & R&D Team for the New Drug of Oriental Medicine (BK21), Daegu Hanny University)
  • 투고 : 2012.04.30
  • 심사 : 2012.07.19
  • 발행 : 2012.07.30

초록

Genistein은 대두 및 그들의 부산물에 풍부하게 존재하는 isoflavone의 일종으로 정상세포에서는 독성을 나타내지 않는 범위에서 다양한 in vitro 및 in vivo 모델에서 암세포의 증식을 효과적으로 억제할 수 있는 천연물로 알려져 있다. 본 연구에서는 MCF-7 및MDA-MB-231 유방암세포에서 matrix metalloproteinases (MMPs)의 활성 및 발현과 침윤성에 미치는 genistein의 영향을 조사하였다. 본 연구의 결과에 의하면 genistein은 12-O-tetradecanoyl phorbol-13-acetate (TPA) 처리에 의하여 활성화된 MMP-2 및 -9의 활성을 유의적으로 차단하였으며, 이는 전사 및 번역 수준에서 MMP-2 및 -9의 발현 억제와 연관성이 있었다. 또한 matrigel invasion assay를 통하여 genistein은 두 유방암세포의 침윤성을 완벽하게 차단하였음을 관찰하였으며, 이러한 효과는 genistein의 세포독성 효과에 의한 것이 아니었음을 알 수 있었다. 비록 in vivo 동물 실험을 통한 부가적인 연구의 필요성이 있으나, 본 연구의 결과는 genistein이 암의 전이를 억제할 수 있는 효과적인 식이 소재임을 보여주는 것이다.

Genistein, a predominant isoflavone, has been shown to inhibit the growth of various cancer cells in vitro and in vivo without toxicity to normal cells. In the present study, we investigated the effects of genistein on the activity and the expression of matrix metalloproteinases (MMPs) in MCF-7 and MDA-MB-231 human breast adenocarcinoma cells. Our findings showed that MMP-9 and -2 activation was significantly increased in response to 12-O-tetradecanoyl phorbol-13-acetate (TPA). However, the increased activities of MMP-9 and -2 in TPA-treated cells were concentration-dependently inhibited by treatment with genistein, and this was also correlated with a decrease in the expression of their mRNA and proteins. In addition, a matrigel invasion assay showed that genistein reduced TPA-induced invasion of MCF-7 and MDA-MB-231 cells. Although further in vivo studies are needed, these results suggest that genistein treatment may inhibit tumor cell invasion and, therefore, act as a dietary source to decrease the risk of cancer metastasis.

키워드

참고문헌

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피인용 문헌

  1. Effect of Anti-oxidant, Anti-inflammatory and Anti-invasive of PMA-induced Matrix Metalloproteinase (MMP-2) and MMP-9 Activities of Water Extract and Solvent Fractions of Saururus Chinensis vol.26, pp.5, 2016, https://doi.org/10.5352/JLS.2016.26.5.584