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Up-Regulation of NAG-1 and p21 Genes by Sulforaphane

브로콜리 유래 sulforaphane에 의한 NAG-1과 p21 유전자의 발현 조절

  • 정병걸 ((주) 넨시스) ;
  • 김순영 (국립안동대학교 자연과학대학 생명과학과) ;
  • 이건주 (국립안동대학교 자연과학대학 생명과학과) ;
  • 김종식 (국립안동대학교 자연과학대학 생명과학과)
  • Received : 2011.11.17
  • Accepted : 2012.02.17
  • Published : 2012.03.30

Abstract

We investigated the anti-proliferative activity of sulforaphane and expression changes of NAG-1 and p21 genes in response to sulforaphane treatment in human colorectal HCT116 cells. The results showed that sulforaphane decreased cell viabilities in a dose-dependent manner and induced expression of NAG-1 and p21 proteins in a dose-dependent and time-dependent manner. In addition, we found that NAG-1 expression by sulforaphane was not dependent on the presence of p53, whereas p21 expression was dependent on p53 presence. The results indicated that up-regulation of NAG-1 was not related with the activity of a dietary histone deacetylase inhibitor of sulforaphane. ATF3 induction was detected from 2 hr after sulforaphane treatment, indicating that ATF3 could be a transcription factor to up-regulate NAG-1 expression. The results of this study may help to increase our understanding of the molecular mechanism of anti-cancer activity mediated by sulforaphane in human colorectal cancer cells.

본 연구에서는 대장암 세포주 모델에서 브로콜리 유래 sulforaphane에 의한 항 성장 활성과 항암 단백질 NAG-1과 p21의 발현 및 발현 조절에 대해서 연구하였다. 그 결과, 처리한 sulforaphane의 농도가 증가됨에 따라 세포사멸이 증가되었고, 세포 생존율은 감소하였다. 또한, sulforaphane에 의한 항암 단백질 NAG-1과 p21의 발현증가를 농도별, 시간대별로 확인한 결과, 두 단백질 모두 sulforaphane 농도와 처리시간 의존적으로 발현이 증가됨을 확인하였다. Sulforaphane에 의한 NAG-1과 p21의 발현의 p53 의존성을 연구한 결과, p21의 발현은 p53에 의존적 이지만 NAG-1의 발현은 p53에 비 의존적인 것으로 생각된다. 또한, sulforaphane이 dietary histone deacetylase inhibitor로서 NAG-1의 발현을 증가시킬 가능성은 매우 미미한 것으로 생각된다. 전사조절인자인 ATF3의 발현을 sulforaphane을 시간대 별로 처리한 후 확인한 결과, 2시간째부터 발현이 증가되어 NAG-1의 발현 보다 먼저 증가됨을 확인하였다. 이러한 연구 결과는 sulforaphane의 항암 기능을 이해하는 새로운 기전을 제시해 줄 것으로 기대된다.

Keywords

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