생명과학회지 (Journal of Life Science)

  • 제19권12호
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  • Pages.1787-1793
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  • 2009
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  • 1225-9918(pISSN)
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  • 2287-3406(eISSN)
한국생명과학회 (Korean Society of Life Science)
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Caffeic acid phenethyl ester의 처리에 의한 NSAID activated gene-1의 과대발현

Over-expression of NSAID Activated Gene-1 by Caffeic Acid Phenethyl Ester

  • 장민정 (안동대학교 자연과학대학 생명과학과) ;
  • 김효은 (안동대학교 자연과학대학 생명과학과) ;
  • 손성민 (안동대학교 자연과학대학 생명과학과) ;
  • 김민정 (안동대학교 자연과학대학 생명과학과) ;
  • 서을원 (안동대학교 자연과학대학 생명과학과) ;
  • 김영호 (경북대학교 자연과학대학 미생물학과) ;
  • 김종식 (안동대학교 자연과학대학 생명과학과)
  • Jang, Min-Jeong (Dept. of Biological Sciences, Andong National University) ;
  • Kim, Hyo-Eun (Dept. of Biological Sciences, Andong National University) ;
  • Son, Seong-Min (Dept. of Biological Sciences, Andong National University) ;
  • Kim, Min-Jeong (Dept. of Biological Sciences, Andong National University) ;
  • Seo, Eul-Won (Dept. of Biological Sciences, Andong National University) ;
  • Kim, Young-Ho (Dept. of Microbiology, Kyungpook National University) ;
  • Kim, Jong-Sik (Dept. of Biological Sciences, Andong National University)
  • 발행 : 2009.12.30
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초록

파이토케미칼의 일종인 CAPE가 암세포 생장에 미치는 영향과 유전자 발현을 연구하기 위하여, 인간 대장암 세포주 HCT116에 CAPE를 처리하였다. CAPE의 처리는 농도 의존적으로 암 세포 생존율을 감소시키고, 세포사멸을 유도함을 확인하였다. CAPE에 의해 차별적으로 발현되는 유전자를 분석하기 위하여, oligo DNA microarray 실험을 수행하였다. 그 결과, $20{\mu}M$ CAPE를 24시간 동안 처리한 경우, 2배 이상 발현이 증가되는 유전자 266개, 2배 이상 발현이 감소되는 유전자 143개를 확인하였다. 발현이 증가되는 유전자중 3개(NAG-1, p21, GADD45A)를 선택하여, RT-PCR을 수행하였다. 그 결과, 모든 유전자의 발현이 마이크로어레이 실험결과와 일치하였다. 또한, CAPE를 농도 의존적으로 처리한 후, NAG-1 유전자와 단백질의 발현을 확인한 결과, mRNA 수준과 단백질 수준에서의 발현양상이 동일함을 확인하였다. 게다가, CAPE를 포함한 5개의 다른 종류의 파이토케미칼(resveratrol, genistein, daidzein, capsaicin)을 처리한 경우, 처리한 모든 파이토케미칼에 의해 NAG-1 유전자의 발현이 증가됨을 확인하였다. 이중 CAPE가 가장 낮은 농도의 처리임에도 불구하고 NAG-1의 발현을 가장 강하게 유도하였다. 결론적으로 이러한 연구결과는 CAPE에 의한 세포사멸은 항암유전자인 NAG-1의 과대발현과 밀접한 관련이 있음을 의미한다.

To investigate whether caffeic acid phenethyl ester (CAPE) could affect cancer cell viabilities and gene expression, human colorectal HCT116 cells were incubated with CAPE. CAPE decreased cancer cell viabilities and induced apoptosis in a dose-dependent manner. To analyse differently expressed genes by CAPE, we performed oligo DNA microarray analysis. We found that 266 genes were up-regulated more than twofold, whereas 143 genes were down-regulated more than twofold by 24 hr of treatment with $20{\mu}M$ CAPE. Among the up-regulated genes, we selected 3 genes (NSAID activated gene-1 [NAG-1], cyclin-dependent kinase inhibitor 1A [CDKN1A, p21] and growth arrest and DNA-damage-inducible alpha [GADD45A]) and performed reverse-transcription PCR to confirm microarray data. In addition, we found that CAPE increased NAG-1 gene and NAG-1 protein expression in a dose-dependent manner. And, several other phytochemicals (resveratrol, genistein, daidzein and capsaicin) also could induce NAG-1 expression in human colorectal HCT116 cells. However, CAPE was the highest inducer of NAG-1, even in low concentrations. Overall, these results imply that cancer cell death by CAPE is closely related with over-expression of NAG-1.

키워드

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  2. Up-Regulation of NAG-1 and p21 Genes by Sulforaphane vol.22, pp.3, 2012, https://doi.org/10.5352/JLS.2012.22.3.360
  3. Anti-Proliferative Activities of Solid-State Fermented Medicinal Herbs Using Phellinus baumii against Human Colorectal HCT116 Cell vol.20, pp.8, 2010, https://doi.org/10.5352/JLS.2010.20.8.1268
  4. Effects of Genistein on Cell Proliferation and Adipogenesis in Mouse 3T3-L1 Preadipocytes vol.22, pp.1, 2012, https://doi.org/10.5352/JLS.2012.22.1.49