Diallyl Disulfide Inhibits N-acetyltransferase Activity and Gene Expression in Human Lung CancerA549 Cells

二丙烯基二硫化物抑制人類肺癌細胞A549的N-乙醯轉移酵素之活性和基因表現

夏德樁(Te-Chun Hsia) ； 林景彬(Jing-Pin Lin) ； 李德茂(Te-Mao Li) ； 袁上雯(Shang-Wen Yuan) ； 鍾景光(Jing-Gung Chung)

《Mid-Taiwan Journal of Medicine》 9卷3期 (2004/09) Pp. 161-168

https://doi.org/10.6558/MTJM.2004.9(3).4

摘要

目的 N-乙醯轉移酵素（NAT）之活性決定個體乙醯轉移的快或慢，被認為影響個體因環境暴露而產生癌症。二丙烯基二硫化物為大蒜主要成分之一，以往被報告含有抗腫瘤的活性。本研究檢測二丙烯基二硫化物是否能夠抑制人類肺癌細胞株N-乙醯轉移酵素（NAT）酵素活性及其基因表現（NAT mRNA）。
方法 利用高壓層析儀檢測二胺螢素（AF）乙醯化和未乙醯化的量來決定N-乙醯轉移酵素（NAT）的活性。NAT蛋白量則利用流式細胞計數儀分析。 NAT mRNA 基因的表現則利用PCR和cDNA晶片檢測。
結果 二丙烯基二硫化物減少人類肺癌細胞對二肢螢素（AF）的乙醯化，而且有劑量依存的關係。由流式細胞計數儀分析顯示，二丙烯基二硫化物降低NAT酵素的量。由 PCR 和 cDNA 晶片的實驗顯示，二丙烯基二硫化物可抑制NAT之基因表現。
結論 本研究結果推論二丙烯基二硫化物抑制人類肺癌細胞NAT之基因表現，導致NAT酵素量減少，因而造成AF的N-乙醯化量減少。

關鍵字

cDNA晶片 ； 二丙烯基二硫化物 ； 人類肺癌細胞株 ； N-乙醯轉移酵素 ； 二胺螢素

並列摘要

Objectives. Acetylators are believed to affect cancer risk related to environmental carcinogen exposure. Individuals can be identified as slow or rapid acetylators by measuring NAT activity. Diallyl disulfide (DADS), one of the major components of garlic (Allium sativum), has been reported to exhibit anti-neoplasm activity. In this study, we investigated the inhibitory effects of DADS on NAT activity and gene expresseion (NAT mRNA) in human lung A549 cancer cells.
Methods. The amounts of N-acety-2-aminofluorene (AAF) and 2-aminofluorene (AF) were measured by high performance liquid chromatography before determining NAT activity. The amounts of NAT enzymes were examined and analyzed by flow cytometry. NAT gene expression(NAT mRNA) was examined by polymerase chain reaction and cDNA microarray.
Results. DADS decreased the N-acetylation of AF in human lung A549 cancer cells in a dose-dependent manner. Flow cytometric analysis indicated that DADS decreased the levels of NATprotein in A549 cells. PCR and cDNA microarray experiments showed that DADS inhibited NAT mRNA expression in A549 cells.
Conclusions. DADS affected NAT activity by inhibiting gene expression (NAT mRNA); the result was a reduction in protein levels of NAT in A549 cells.

並列關鍵字

cDNA microarray ； diallyl disulfide (DADS) ； human lung cancer cell line ； N-acetyltransferase(NAT) ； 2-aminofluorene (AF)