Gingernone A藉由增加細胞內活性氧物種生成及粒線體細胞凋亡路徑誘發SK-Hep-1細胞凋亡

Gingernone A-induced Apoptosis in SK-Hep-1 Cells is Mediated Via Increased Reactive Oxygen Species (ROS) Production and the Mitochondria-Associated Apoptotic Mechanisms

滿庭芳(Ting-Fang Mann) ； 陳中一(Chung-Yi Chen) ； 陳志良(Chi-Liang Chern) ； 劉崇喜(Shorong-Shii Liou) ； 尹順君(Shuenn-Jiun Yiin)

《大仁學報》 47期 (2015/09) Pp. 1-14

摘要

使用天然物來預防癌症發被認為是極具潛力的方式，本研究發現gingerenone A會透過誘發細胞凋亡進而抑制細胞生長，在細胞凋亡路徑探討方面，我們以外部路徑抑制劑(NOK-1, DR5 chimeric protein, and Etanercept)前處理細胞，發現並不能抑制gingerenone A誘發的細胞凋亡，關於粒線體調控的路徑方面，實驗結果發現gingerenone A會增加細胞內活性氧生成，降低粒線體膜電位及釋放cytochrome c至細胞質內，進而引發細胞凋亡，綜合上述，本研究結果顯示gingerenone A會藉由增加細胞內活性氧產生，活化粒線體調控的細胞凋亡路徑，導致細胞凋亡。

關鍵字

生薑 ； 細胞凋亡 ； 活性氧

並列摘要

Chemoprevention by the use of naturally occurring substances is becoming a promising strategy to prevent cancer. In this study, gingernone A (Gin A) was found to elicit a concentration-dependent growth impediment. The demise of these cells induced by Gin A was apoptotic in nature, exhibiting a concentration-dependent increase in sub G1 fraction. In order to clarify whether death receptor-mediated pathways were involved in Gin A-induced apoptosis, the inhibitory effects of NOK-1, DR5 chimeric protein, and Etanercept on Gin A-induced apoptosis were examined. The results showed that these inhibitors could not prevent cells from becoming apoptosis-prone. As to the role of mitochondria in Gin A-induced apoptosis, we found that Gin A-treated cells displayed transient increase of ROS during the earlier stage of the experiment, followed by the disruption of mitochondrial transmembrane potential (ΔΨm). Subcellular fractionation analysis further revealed a rapid increase of cytochrome c in cytoplasm. Taken together, our data suggest that ROS plays an essential role in Gin A-induced apoptosis via mitochondrial pathways.

並列關鍵字

Ginger ； apoptosis ； reactive oxygen species

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