The molecular mechanism of ellagic acid-induced apoptotic cell death in human lung cnacer cells
| Autor: | 林亮豪 |
|---|---|
| Rok vydání: | 2005 |
| Druh dokumentu: | 學位論文 ; thesis |
| Popis: | 93 Ellagic acid (EA) is a phenolic compound isolated from fruits and nuts including strawberry raspberries and walnuts. EA has a proven, anti-mutation and anti-cancer properties. However, the molecular mechanisms of EA on cell growth and death of cancer cells have not been fully defined. In this study, we found that treatment of human lung adenocarcinoma A549 cells with 100 μM EA caused a time- and dose-dependent cell deaths. Data from DAPI staining and TUNEL assay showed that EA triggered an apoptotic cell death process. Moreover, EA induced reactive oxygen species (ROS) generation and membrane permeability transition (MPT) change. EA treatment caused an increase in the expression levels of TRAIL-R1 (DR4) death receptor but did not alter the levels of other death receptors and Bcl-2 family molecules. Administration of EA resulted in the activation of caspases-2, -3, -8 and -9. The inhibitors of caspase-3, and caspase-8 markedly prevented the cell death induced by EA. Moreover, increase in the level of phosphorylated ERK and decrease in phosphorylated AKT and survivin were observed in EA-treated A549 cells. Preincubation with ERK inhibitor, markedly promoted the EA-induced apoptosis. In addition, A549/clone-3 cells (less p53) and A549/p53-siRNA-14 cells (p53 undetectable) were more resistant to EA. This event were accompanied by survivin regulation and p38 phosphorylation than Parental A549 cells. Taken together, our results demonstrate that EA-triggered apoptosis may be via a death receptor (TRAIL-R1,DR4)-dependent caspase-8/caspase-3 activation pathway. In addition, generation of ROS, down-regulation of AKT and survivin may also contribute to apoptosis in EA-treated A549 cells. |
| Databáze: | Networked Digital Library of Theses & Dissertations |
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