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請使用永久網址來引用或連結此文件:
https://irlib.pccu.edu.tw/handle/987654321/20958
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| 題名: | Plumbagin, Isolated from Plumbago zeylanica, Induces Cell Death through Apoptosis in Human Pancreatic Cancer Cells |
| 作者: | Chen, CA (Chen, Chien-An)
Chang, HH (Chang, Hen-Hong)
Kao, CY (Kao, Chung-Yu)
Tsai, TH (Tsai, Tung-Hu)
Chen, YJ (Chen, Yu-Jen) |
| 貢獻者: | 運教所 |
| 關鍵詞: | Plumbagin
Pancreatic cancer
Apoptosis
Mitochondria |
| 日期: | 2009 |
| 上傳時間: | 2011-12-09 15:21:30 (UTC+8) |
| 摘要: | Background and Aims: Pancreatic cancer is one of the most resistant malignancies. Several studies have indicated that plumbagin isolated from Plumbago zeylanica possesses anticancer activity. However, its antitumor effects against pancreatic cancer have not been explored. Methods: We investigated the effect of plumbagin on the growth of human pancreatic carcinoma cells and its possible underlying mechanisms. Results: Plumbagin inhibited the growth of Panc-1 and Bxpc-3 cells in a dose-dependent and time-dependent manner. Liu's staining and transmission electron microscopy demonstrated morphological changes resembling apoptosis in Panc-1 cells treated with plumbagin. The degree of apoptosis was assessed by measuring the proportions of sub-G 1, annexin V+/propidium iodide-, and terminal-deoxynucleotidyl- transferase-mediated-nick-end labeling (TUNEL)+ cells, and a significant increment in apoptotic cells was observed. Exposure to plumbagin caused the upregulation of Bax, a rapid decline in mitochondrial transmembrane potential, apoptosis-inducing factor overexpression in cyto sol, and the cleavage of procaspase-9 and poly ADP-ribose polymerase. Activation of caspase-3, but not caspase-8, was evidenced by fluorometric substrate assay. Pretreatment with caspase inhibitors did not block plumbagin-induced apoptosis. Alternatively, it is possible that plumbagin down-regulated phosphoinositide 3-kinase activity through a negative feedback mechanism. In an orthotopic pancreatic tumor model, plumbagin markedly inhibited the growth of Panc-1 xenografts without any significant effect on leukocyte counts or body weight. Conclusion: Plumbagin may induce apoptosis in human pancreatic cancer cells primarily through the mitochondria-related pathway followed by both caspase-dependent and caspase-independent cascades. It indicates that plumbagin can be potentially developed as a novel therapeutic agent against pancreatic cancer. Copyright (C) 2010 S. Karger AG, Basel and IAP |
| 顯示於類別: | [運動教練研究所] 期刊論文
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