Andrographolide down-regulates hypoxia-inducible factor-1α in human non-small cell lung cancer A549 cells

doi:10.1016/j.taap.2010.11.014

中山醫學大學機構典藏 CSMUIR > 醫學科技學院 > 醫學檢驗暨生物技術學系暨碩士班 > 期刊論文 > Item 310902500/4396

Please use this identifier to cite or link to this item: https://ir.csmu.edu.tw:8080/ir/handle/310902500/4396

Title:	Andrographolide down-regulates hypoxia-inducible factor-1α in human non-small cell lung cancer A549 cells
Authors:	Lin, Hui-Hsuan Wang, Cheng-Kun Hsuan, Shu-Wen Tsai, Chia-Wen Chou, Fen-Pi Wang, Chau-Jong Chen, Jing-Hsien
Contributors:	中山醫學大學醫學檢驗暨生物技術學系
Keywords:	Andrographolide Non-small cell lung cancer A549 cell Hypoxia-inducible factor-1α Prolyl hydroxylase Vascular endothelial growth factor
Date:	2010-11-25
Issue Date:	2012-08-01T08:12:47Z (UTC)
ISSN:	0041-008X
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.
URI:	https://ir.csmu.edu.tw:8080/ir/handle/310902500/4396 http://dx.doi.org/10.1016/j.taap.2010.11.014
Relation:	Toxicology and Applied Pharmacology Volume 250, Issue 3, 1 February 2011, Pages 336–345
Appears in Collections:	[醫學檢驗暨生物技術學系暨碩士班] 期刊論文

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