|
English
|
正體中文
|
简体中文
|
Items with full text/Total items : 17939/22958 (78%)
Visitors : 7389669
Online Users : 215
|
|
|
Loading...
|
Please use this identifier to cite or link to this item:
https://ir.csmu.edu.tw:8080/ir/handle/310902500/10746
|
Title: | Andrographolide down-regulates hypoxia-inducible factor-1α in human non-small cell lung cancer A549 cells. |
Authors: | Lin, HH Tsai, CW Chou, FP Wang, CJ Hsuan, SW Wang, CK Chen, JH |
Contributors: | 中山醫學大學 |
Keywords: | Andrographolide;Non-small cell lung cancer A549 cell;Hypoxia-inducible factor-1α;Prolyl hydroxylase;Vascular endothelial growth factor |
Date: | 2011 |
Issue Date: | 2015-05-08T07:29:06Z (UTC)
|
ISSN: | 0041-008X |
Abstract: | Abstract
Andrographolide (Andro), a diterpenoid lactone isolated from a traditional herbal medicine Andrographis paniculata, is known to possess multiple pharmacological activities. In our previous study, Andro had been shown to inhibit non-small cell lung cancer (NSCLC) A549 cell migration and invasion via down-regulation of phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway. Here we demonstrated that Andro inhibited the expression of hypoxia-inducible factor-1α (HIF-1α) in A549 cells. HIF-1α plays an important role in tumor growth, angiogenesis and lymph node metastasis of NSCLC. The Andro-induced decrease of cellular protein level of HIF-1α was correlated with a rapid ubiquitin-dependent degradation of HIF-1α, and was accompanied by increased expressions of hydroxyl-HIF-1α and prolyl hydroxylase (PHD2), and a later decrease of vascular endothelial growth factor (VEGF) upon the treatment of Andro. The Andro-inhibited VEGF expression appeared to be a consequence of HIF-1α inactivation, because its DNA binding activity was suppressed by Andro. Molecular data showed that all these effects of Andro might be mediated via TGFβ1/PHD2/HIF-1α pathway, as demonstrated by the transfection of TGFβ1 overexpression vector and PHD2 siRNA, and the usage of a pharmacological MG132 inhibitor. Furthermore, we elucidated the involvement of Andro in HIF-1α transduced VEGF expression in A549 cells and other NSCLC cell lines. In conclusion, these results highlighted the potential effects of Andro, which may be developed as a chemotherapeutic or an anti-angiogenesis agent for NSCLC in the future.
Copyright © 2010 Elsevier Inc. All rights reserved. |
URI: | https://ir.csmu.edu.tw:8080/ir/handle/310902500/10746 http://dx.doi.org/10.1016/j.taap.2010.11.014 |
Relation: | Toxicol Appl Pharmacol. 2011 Feb 1;250(3):336-45. |
Appears in Collections: | [生化微生物免疫研究所] 期刊論文
|
Files in This Item:
File |
Description |
Size | Format | |
index.html | 期刊論文 | 0Kb | HTML | 370 | View/Open |
|
All items in CSMUIR are protected by copyright, with all rights reserved.
|