The Korean Journal of Food And Nutrition (한국식품영양학회지)

The Korean Society of Food and Nutrition (한국식품영양학회)
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3,4-Dihydroxytoluene Inhibits Epidermal Growth Factor-induced Cell Transformation in JB6 P+ Mouse Epidermal Cells by Suppressing Raf-1

3,4-Dihydroxytoluene의 Raf-1 신호전달체계 억제를 통한 암예방 효능

  • Kim, Ji An (School of Food Science and Biotechnology, Kyungpook National University) ;
  • Kim, Ji Hye (School of Food Science and Biotechnology, Kyungpook National University) ;
  • di Ruccio, Eric (School of Food Science and Biotechnology, Kyungpook National University) ;
  • Kang, Nam Joo (School of Food Science and Biotechnology, Kyungpook National University)
  • Received : 2015.01.21
  • Accepted : 2015.02.16
  • Published : 2015.02.28
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Abstract

In summary, the rutin metabolite DHT significantly reduced EGF-induced neoplastic transformation in JB6 P+ cells. This inhibition was mediated mainly by blocking the Raf/MEK/ERK signaling pathway and subsequent suppression of AP-1 activities. DHT attenuated Raf-1 kinase activity by directly binding to Raf-1 in vitro and ex vivo. Taken together, these results suggest that Raf-1 may be a critical molecular target to suppress DHT-induced neoplastic transformation, which is mainly attributable to the chemopreventive potential of several foods containing rutin.

이전 연구들에서 rutin과 quercetin을 포함한 여러 flavonoids의 암예방 활성이 보고되었으나, rutin의 경우 섭취 시 체내에서 HVA, HPAA, DHT라는 대사체로 변형되어 흡수된다. 그러나, 이들 대사체와 관련한 암예방 효능 및 그 분자생물학적 작용기작에 대한 연구 결과는 보고된 바가 없어, 본 연구에서 이를 규명하였다. DHT는 EGF로 유도된 세포 변형을 억제하였으며, AP-1 전사인자의 활성 또한 억제하였다. DHT는 Raf-1 효소 활성을 효과적으로 저해하므로서 MEK 및 ERK의 인산화를 억제하였으며, Raf-1과 ATP는 비경쟁적으로 직접 결합하여 Raf-1 효소 활성을 저해한다는 사실을 밝혀내었다. 이와는 대조적으로, rutin은 EGF로 유도된 세포 변형, AP-1 활성, ERK 신호전달체계, Raf-1 효소 활성을 억제하지 못하였다. 이상의 연구결과는 DHT의 암예방 활성이 발암과정과 밀접한 연관이 있는 Raf-1 효소 활성을 억제하여 세포 변형을 억제하는 것과 관련되어 있다는 것을 제시한다.

Keywords

References

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