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標題: 白藜蘆醇在人類肺腺癌細胞A549中經由活性氧化物質引發的內質網壓力造成細胞凋亡
Resveratrol induces ROS-dependent ER stress-mediated apoptosis in human lung adenocarcinoma A549 cell line
作者: 徐君怡
Hsu, Chun-Yi
關鍵字: Resveratrol
出版社: 生物醫學研究所
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摘要: Resveratrol, a naturally occurring polyphenol, exhibits antioxidant, antiaging, and anticancer activity. Recent experimental evidence indicating that the compound at significantly higher concentrations is a strong inducer of intracellular reactive oxygen species (ROS). We investigated the effect of resveratrol on human lung adenocarcinoma cell line, in particular its ability to induce intracellular reactive oxygen species production. Treatment of A549 human adenocarcinoma cells with resveratrol was found to induce a number of signature ER stress markers; phosphorylation of eukaryotic initiation factor-2α (eIF-2α), ER stress-specific XBP1 splicing , CCAAT/enhancer-binding protein homologous protein (CHOP) and activating transcription factor 3(ATF3). Finally, Resveratrol-induced ER stress-mediated apoptosis was significantly reduced by the antioxidant N-acetyl-L-cysteine (NAC). Taken together, the present studies suggest that induction of ROS may be involved, at least in part, in resveratrol-induced apoptosis
白藜蘆醇是一種天然的多酚類化合物,自然界中常見於葡萄葉表皮、漿果果皮和各種常見的中藥中,具有抗氧化、抗老化與抗癌等多種功效,本篇論文主要探討白藜蘆醇對於人類肺腺癌細胞株A549產生的影響,特別是對於白藜蘆醇如何使細胞內活性氧化物產生。首先我們藉由流式細胞儀偵測細胞內活性氧化物含量發現在白藜蘆醇的處理下人類肺腺癌細胞株A549確實會產生活性氧化物,並且利用西方點墨法及半定量反轉錄聚合連鎖反應證實內質網壓力中IRE-1與PERK等路徑活化,增加內質網壓力相關蛋白質表現,為了證實白藜蘆醇誘發的活性氧化物能引發內網壓力,使用抗氧化劑N-acetyl-L-cysteine (NAC) 處理細胞株,發現能有效降低白藜蘆醇引發的內質網壓力與細胞凋亡等現象,另外將CHOP及ATF3 分別Knockdown,發現細胞凋亡現象減少並且CHOP及ATF3可能有互相調控的情形,顯示由白藜蘆醇引發的內質網壓力會造癌細胞的細胞凋亡,並且進一步的探討CHOP及ATF3互相調控的機制。 由本實驗結果得知在白藜蘆醇的處理之下人類肺腺癌細胞株A549會產生活性氧化物並引發內質網壓力產生,最後引發癌細胞細胞凋亡。 因此白藜蘆醇具有發展成抗癌藥物的潛力,本實驗提出一些相關的影響路徑,更可以為未來藥物設計提供一些方向。
其他識別: U0005-1608201117002200
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