http://scholars.ntou.edu.tw/handle/123456789/23815
Title: | 鼠尾草酸對人類神經母細胞瘤IMR-32細胞株細胞週期之影響 | Other Titles: | Effect of Carnosic Acid on the Induction of Cell Cycle Arrest in Human Neuroblastoma IMR-32 Cells | Authors: | 林家媛 蔡佳文 |
Keywords: | 鼠尾草酸;活性氧化物質;細胞週期;p38激酶;人類神經母細胞瘤IMR- 32細胞株;carnaslc acid;reactive oxygen specles;cell cycle;p38 klnase;human neuroblastoma IMR-32 cells | Issue Date: | Dec-2011 | Publisher: | 台灣營養學會 | Journal Volume: | 36 | Journal Issue: | 4 | Start page/Pages: | 116 - 124 | Source: | 臺灣營養學會雜誌 Nutritional Sciences Journal | Abstract: | 鼠尾草酸(carnosic acid, CA)為迷迭香中的二萜類(diterpene),由於我們先前的研究發現CA會透過增加活性氧化物質(reactive oxygen species, ROS)而活化p38蛋白,以促進人類神經母細胞瘤(neuroblastoma)IMR-32細胞發生凋亡。因此,本研究欲探討CA減少IMR-32細胞生長是否與ROS和p38路徑影響其細胞週期有關。IMR-32細胞以30 μM的CA處理12-60小時,流式細胞儀結果顯示在CA處理24小時後,細胞滯留在GO/G1期的比例顯著地增加,而且CA隨處理濃度的增加而降低週期素(cyclins)中的cyclin D1和cyclinD3以及週期素激酶(cyclin-dependent kinases, CDKs)中的CDK4和CDK6蛋白表現,然而CA對於細胞週期抑制性蛋白(cyclin dependent kinase inhibitors, CDKls)中p21蛋白的表現卻隨著濃度的增加而增加。另外,細胞若先處理抗氧化劑N-乙醯基半胱氯酸(N-acetylcysteine,NAC)或進行p38 siRNA實驗,則會抑制CA增加p21蛋白的能力,並回復CA抑制CDK4蛋白的能力。結論:CA可能透過調節p21和CDK4蛋白表現,使IMR-32細胞停滯在GO/G1期,且此路徑可能與ROS和p38路徑有關,因此,CA未來可能可發展為抵抗神經母細胞瘤的化學預防治療策略。Carnosic acid (CA) is a phenolic diterpene obtained from rosemary (Rosmarinus officinalis) . Our previous study indicated that CA induced apoptotic cell death through reactive oxygen species (ROS) -mediated phosphorylation of p38 in human neuroblastoma IMR-32 cells. In this study, we explored whether CA-reduced cell viability was associated with cell-cycle arrest through ROS generation and the p38 pathway. IMR-32 cells were treated with 30 μM CA for 12~60 h. A flow cytometric analysis indicated that cells were significantly arrested in the GO/G1 phase when treated with CA for 24 h (p < 0.05). Immunoblotting suggested that CA decreased the levels of cell-cycle regulatory proteins such as cyclin D1, cyclin D3, CDK4, and CDK6 proteins, while increasing the level of p21 protein. Pretreatment with the antioxidant, N-acetylcysteine (NAC), or p38 siRNA inhibited CAinduced p21 expression, whereas it reversed CA-decreased CDK4 expression. In conclusion, CA induced ROS generation and p38 activation, which in turn modulated the protein expressions of p21 and CDK4, and induced GO/G1 cell-cycle arrest in IMR-32 cells. Therefore, CA has the potential to be developed as a therapeutic agent against neuroblastoma. |
URI: | http://scholars.ntou.edu.tw/handle/123456789/23815 | DOI: | 10.6691/NSJ.201112_36(4).0003 |
Appears in Collections: | 食品科學系 |
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