Journal of Life Science (생명과학회지)

Korean Society of Life Science (한국생명과학회)
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EGCG induces Apoptosis under Hypoxic State in B16F10 Melanoma Cancer Cells

저산소증 상태에서 B16F10 피부암 세포에 EGCG를 처리하였을 때의 apoptosis 효과

  • Kim, Yoon-Yi (Department of Biological Sciences, Hannam University Daedeok Valley Campus) ;
  • Kim, In-Seop (Department of Biological Sciences, Hannam University Daedeok Valley Campus) ;
  • Park, Ock-Jin (Department of Food and Nutrition, Hannam University Daedeok Valley Campus) ;
  • Kim, Young-Min (Department of Biological Sciences, Hannam University Daedeok Valley Campus)
  • 김윤이 (한남대학교 생명나노과학대학 생명과학과) ;
  • 김인섭 (한남대학교 생명나노과학대학 생명과학과) ;
  • 박옥진 (한남대학교 생명나노과학대학 식품영양학과) ;
  • 김영민 (한남대학교 생명나노과학대학 생명과학과)
  • Received : 2010.11.04
  • Accepted : 2010.12.03
  • Published : 2011.02.28
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Abstract

EGCG, catechins in green tea, is a kind of phytochemical. Through the regulation of signal pathways, EGCG has been known to show anti-oxidant and anti-tumor effects in cells. In this study, we investigated the apoptotic effects of EGCG through AMP-activated protein kinase (AMPK) signal pathways, including hypoxia inducible factor-1 alpha (HIF-$1{\alpha}$). The experiments were performed in B16F10 melanoma cells in a hypoxic state. AMPK is activated by ATP consumption such as nutrient deficiency, exercise, heat shock, etc. The activated AMPK that plays an important role as an energy sensor inhibits proliferation of cancer cells, as well as inducing apoptosis. HIF-$1{\alpha}$, the primary transcriptional regulator of the response to oxygen deprivation, plays a critical role in modulating tumor growth and angiogenesis in a hypoxic state. The apoptotic effects of EGCG were studied in B16F10 cells in a hypoxic state. The results show that EGCG inhibits the transcriptional activity of HIF-$1{\alpha}$ and induces apoptosis. These observations suggest that EGCG may exert inhibitory effects of angiogenesis and control tumor cell growth in hypoxic melanoma cells.

파이토케미컬의 일종인 EGCG는 녹차의 카테킨 성분으로, 세포 내 신호 경로 조절을 통하여 항산화, 항암효과를 나타내는 것으로 알려져 있다. 본 연구에서는 hypoxia 상태인 B16F10 피부암 세포에서 HIF-$1{\alpha}$를 포함한 AMPK의 신호경로를 통하여 EGCG의 apoptosis 유도 효과를 규명하였다. AMPK는 hypoxia, 영양분 결핍, 운동, heat shock 등, 세포 내 ATP의 결핍에 의해서 활성화되며 암세포의 증식을 억제하고 apoptosis를 유도한다. 세포에서 중요한 에너지 센서로서 작용하는 AMPK가 hypoxia 상태의 암세포 내에서는 HIF-$1{\alpha}$의 전사 활성을 유도하는데, HIF-$1{\alpha}$는 hypoxia 상태에서 산소 결핍에 반응하는 첫 번째 전사 조절인자로서 암세포의 생존을 위한 세포내 산소공급과 혈관신생형성을 조절한다. Hypoxia 상태가 아닌 B16F10 세포에서와 hypoxia 상태에서의 B16F10 세포에서 EGCG에 의한 apoptosis 효과를 관찰하였다. 실험 결과, hypoxia 상태에서 EGCG는 더 강한 apoptosis를 유도하며, 혈관신생형성을 조절할 수 있는 HIF-$1{\alpha}$의 전사 활성을 억제시킨다. 이러한 관찰을 통해 EGCG가 hypoxia 상태의 피부암 세포에서 암의 성장과 신생혈관형성을 저해하는 것으로 보인다. 이와 같은 연구는 향후 식품에 첨가된 파이토케미컬을 이용하여 암을 예방하는 연구에서 있어서, 도움이 될 것으로 여겨진다.

Keywords

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