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Title: Andrographolide down-regulates hypoxia-inducible factor-1{alpha} in human non-small cell lung cancer A549 cells

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-1{alpha} (HIF-1{alpha}) in A549 cells. HIF-1{alpha} plays an important role in tumor growth, angiogenesis and lymph node metastasis of NSCLC. The Andro-induced decrease of cellular protein level of HIF-1{alpha} was correlated with a rapid ubiquitin-dependent degradation of HIF-1{alpha}, and was accompanied by increased expressions of hydroxyl-HIF-1{alpha} 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-1{alpha} inactivation, because its DNA binding activity was suppressed by Andro. Molecular data showed that all these effects of Andro might be mediated via TGF{beta}1/PHD2/HIF-1{alpha} pathway, as demonstrated by the transfection of TGF{beta}1 overexpression vector and PHD2 siRNA, and the usage of a pharmacological MG132 inhibitor. Furthermore, we elucidated the involvement of Andro in HIF-1{alpha} transduced VEGF expression in A549 cells and other NSCLC cell lines. Inmore » 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.« less

Authors:
 [1];  [2];  [3];  [4];  [5];  [6];  [5]
  1. School of Medical Laboratory and Biotechnology, Chung Shan Medical University, Taichung, Taiwan (China)
  2. Department of Nutrition, China Medical University, Taichung, Taiwan (China)
  3. Institute of Biochemistry and Biotechnology, Chung Shan Medical University, Taichung, Taiwan (China)
  4. Department of Medical Research, Chung Shan Medical University Hospital, Taichung, Taiwan (China)
  5. Department of Medical Laboratory Science and Biotechnology, College of Medicine and Life Science, Chung Hwa University of Medical Technology, No.89, Wen Hwa 1st St., Rende Shiang, Tainan County 717, Taiwan (China)
  6. E-Chyun Dermatology Clinic, No.70, Sec. 3, Jhonghua E. Rd., East District, Tainan, Taiwan (China)
Publication Date:
OSTI Identifier:
21535231
Resource Type:
Journal Article
Journal Name:
Toxicology and Applied Pharmacology
Additional Journal Information:
Journal Volume: 250; Journal Issue: 3; Other Information: DOI: 10.1016/j.taap.2010.11.014; PII: S0041-008X(10)00446-1; Copyright (c) 2010 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Journal ID: ISSN 0041-008X
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ANGIOGENESIS; CHEMILUMINESCENCE; DNA; ELECTROPHORESIS; GROWTH FACTORS; HUMAN POPULATIONS; LUNGS; LYMPH NODES; NEOPLASMS; BODY; DISEASES; EMISSION; LUMINESCENCE; LYMPHATIC SYSTEM; MITOGENS; NUCLEIC ACIDS; ORGANIC COMPOUNDS; ORGANS; PHOTON EMISSION; POPULATIONS; PROTEINS; RESPIRATORY SYSTEM

Citation Formats

Lin, Hui-Hsuan, Department of Medical Research, Chung Shan Medical University Hospital, Taichung, Taiwan, Tsai, Chia-Wen, Chou, Fen-Pi, Wang, Chau-Jong, Institute of Biochemistry and Biotechnology, Chung Shan Medical University, Taichung, Taiwan, Hsuan, Shu-Wen, Wang, Cheng-Kun, and Chen, Jing-Hsien. Andrographolide down-regulates hypoxia-inducible factor-1{alpha} in human non-small cell lung cancer A549 cells. United States: N. p., 2011. Web. doi:10.1016/j.taap.2010.11.014.
Lin, Hui-Hsuan, Department of Medical Research, Chung Shan Medical University Hospital, Taichung, Taiwan, Tsai, Chia-Wen, Chou, Fen-Pi, Wang, Chau-Jong, Institute of Biochemistry and Biotechnology, Chung Shan Medical University, Taichung, Taiwan, Hsuan, Shu-Wen, Wang, Cheng-Kun, & Chen, Jing-Hsien. Andrographolide down-regulates hypoxia-inducible factor-1{alpha} in human non-small cell lung cancer A549 cells. United States. https://doi.org/10.1016/j.taap.2010.11.014
Lin, Hui-Hsuan, Department of Medical Research, Chung Shan Medical University Hospital, Taichung, Taiwan, Tsai, Chia-Wen, Chou, Fen-Pi, Wang, Chau-Jong, Institute of Biochemistry and Biotechnology, Chung Shan Medical University, Taichung, Taiwan, Hsuan, Shu-Wen, Wang, Cheng-Kun, and Chen, Jing-Hsien. 2011. "Andrographolide down-regulates hypoxia-inducible factor-1{alpha} in human non-small cell lung cancer A549 cells". United States. https://doi.org/10.1016/j.taap.2010.11.014.
@article{osti_21535231,
title = {Andrographolide down-regulates hypoxia-inducible factor-1{alpha} in human non-small cell lung cancer A549 cells},
author = {Lin, Hui-Hsuan and Department of Medical Research, Chung Shan Medical University Hospital, Taichung, Taiwan and Tsai, Chia-Wen and Chou, Fen-Pi and Wang, Chau-Jong and Institute of Biochemistry and Biotechnology, Chung Shan Medical University, Taichung, Taiwan and Hsuan, Shu-Wen and Wang, Cheng-Kun and Chen, Jing-Hsien},
abstractNote = {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-1{alpha} (HIF-1{alpha}) in A549 cells. HIF-1{alpha} plays an important role in tumor growth, angiogenesis and lymph node metastasis of NSCLC. The Andro-induced decrease of cellular protein level of HIF-1{alpha} was correlated with a rapid ubiquitin-dependent degradation of HIF-1{alpha}, and was accompanied by increased expressions of hydroxyl-HIF-1{alpha} 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-1{alpha} inactivation, because its DNA binding activity was suppressed by Andro. Molecular data showed that all these effects of Andro might be mediated via TGF{beta}1/PHD2/HIF-1{alpha} pathway, as demonstrated by the transfection of TGF{beta}1 overexpression vector and PHD2 siRNA, and the usage of a pharmacological MG132 inhibitor. Furthermore, we elucidated the involvement of Andro in HIF-1{alpha} 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.},
doi = {10.1016/j.taap.2010.11.014},
url = {https://www.osti.gov/biblio/21535231}, journal = {Toxicology and Applied Pharmacology},
issn = {0041-008X},
number = 3,
volume = 250,
place = {United States},
year = {Tue Feb 01 00:00:00 EST 2011},
month = {Tue Feb 01 00:00:00 EST 2011}
}