마늘성분 Allicin에 의해 차별적으로 발현되는 유전자군의 발현 분석
Analysis of Differentially Expressed Genes by Allicin in Human Colorectal Cancer Cell.
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본 연구에서는 마늘성분 allicin에 의한 항암 기전 및 화학적 암 예방법의 분자 생물학적 기전을 이해하기 위한 연구의 일환으로, 마늘성분 중의 하나인 allicin이 인체 대장암세포주 HCT116의 증식에 미치는 영향을 확인하였다. allicin 의 처리에 따라 세포사멸이 나타나며 생존율이 감소함을 확인하였다. 또한 oligo DNA microarray 실험을 통하여allicin에 의해 발현되는 유전자 중 발현양의 차이를 보인 유전자중 2배 이상 up-regulation된 유전자는 7,840개, 2배 이상 down-regulation 된 유전자는 10,010개로 각각 분류 되었다. 이 중, ATF3유전자의 발현을 확인하였고, 또 다른 항암유전자인 NAG-1 유전자의 발현을 RT-PCR로 확인하였다. 그 결과, allicin처리에 의해 항암유전자인 ATF3의 발현과NAG1 유전자의 발현이 증가함을 확인하였다. 또한 p53 null HCT116 세포주를 이용하여 allicin에 의한 NAG1 단백질의발현을 확인한 결과, allicin은 p53 유전자 의존적으로 NAG-1 단백질을 발현함을 확인하였다. 결론적으로 allicin은 세포주기나 세포사멸에 관련된 많은 유전자들의 발현 변화를 유도함으로써 암세포 성장억제 활성을 갖는 것으로 사료된다.
Abstract
We investigated anti-cancer and anti-proliferative activity of allicin and analyzed global gene expression changes by allicin treatment in human colorectal HCT116 cells. As a result, allicin decreased cell viabilities in a dose and time-dependent manner and induced apoptosis. Oligo DNA microarray analysis, we found that 7,840 genes were up-regulated more than 2-folds, whereas 10,010genes were down-regulated more than 2-folds by 50 μM allicin treatment. To confirm specific gene expressions,we performed RT-PCR. Consistent with the results of DNA microarray analysis, allicin dramatically induced ATF3 and NAG1 gene expression. Interestingly, NAG-1 protein expression was dependent on p53presence. Taken together, our present results increase the knowledge of the molecular mechanism of anti-cancer and anti-proliferative activity mediated by allciin in human colorectal cancer cell.
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