Next Article in Journal
Marine Bromophenol Derivative 3,4-Dibromo-5-(2-bromo-3,4-dihydroxy-6-isopropoxymethyl benzyl)benzene-1,2-diol Protects Hepatocytes from Lipid-Induced Cell Damage and Insulin Resistance via PTP1B Inhibition
Previous Article in Journal
Four New Sulfated Polar Steroids from the Far Eastern Starfish Leptasterias ochotensis: Structures and Activities
Article Menu

Export Article

Open AccessArticle
Mar. Drugs 2015, 13(7), 4436-4451; doi:10.3390/md13074436

Low Molecular Weight Fucoidan Inhibits Tumor Angiogenesis through Downregulation of HIF-1/VEGF Signaling under Hypoxia

1,†
,
2,3,†
,
4
and
1,5,6,7,*
1
Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei 11483, Taiwan
2
School of Medicine, Tzu Chi University, Hualien 97002, Taiwan
3
Department of Radiation Oncology, Buddhist Tzu Chi General Hospital, Hualien 97002, Taiwan
4
Seafood Technology Division, Fisheries Research Institute, Council of Agriculture, Keelung 20246, Taiwan
5
Institute of Medical Sciences, Tzu Chi University, Hualien 97002, Taiwan
6
Department of Biotechnology, Asia University, Taichung 41354, Taiwan
7
China Medical University Hospital, China Medical University, Taichung 40447, Taiwan
These authors contributed equally to this work.
*
Author to whom correspondence should be addressed.
Academic Editor: Keith B. Glaser
Received: 3 May 2015 / Revised: 15 June 2015 / Accepted: 23 June 2015 / Published: 17 July 2015
View Full-Text   |   Download PDF [5492 KB, uploaded 17 July 2015]   |  

Abstract

Activation of hypoxia-induced hypoxia-inducible factors-1 (HIF-1) plays a critical role in promoting tumor angiogenesis, growth and metastasis. Low molecular weight fucoidan (LMWF) is prepared from brown algae, and exhibits anticancer activity. However, whether LMWF attenuates hypoxia-induced angiogenesis in bladder cancer cells and the molecular mechanisms involved remain unclear. This is the first study to demonstrate that LMWF can inhibit hypoxia-stimulated H2O2 formation, HIF-1 accumulation and transcriptional activity vascular endothelial growth factor (VEGF) secretion, and the migration and invasion in hypoxic human bladder cancer cells (T24) cells. LMWF also downregulated hypoxia-activated phosphorylation of PI3K/AKT/mTOR/p70S6K/4EBP-1 signaling in T24 cells. Blocking PI3K/AKT or mTOR activity strongly diminished hypoxia-induced HIF-1α expression and VEGF secretion in T24 cells, supporting the involvement of PI3K/AKT/mTOR in the induction of HIF-1α and VEGF. Additionally, LMWF significantly attenuated angiogenesis in vitro and in vivo evidenced by reduction of tube formation of hypoxic human umbilical vascular endothelial cells and blood capillary generation in the tumor. Similarly, administration of LMWF also inhibited the HIF-1α and VEGF expression in vivo, accompanied by a reduction of tumor growth. In summary, under hypoxia conditions, the antiangiogenic activity of LMWF in bladder cancer may be associated with suppressing HIF-1/VEGF-regulated signaling pathway. View Full-Text
Keywords: low molecular weight fucoidan; angiogenesis; hypoxia-inducible factor 1 alpha; vascular endothelial growth factor; bladder cancer low molecular weight fucoidan; angiogenesis; hypoxia-inducible factor 1 alpha; vascular endothelial growth factor; bladder cancer
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

Scifeed alert for new publications

Never miss any articles matching your research from any publisher
  • Get alerts for new papers matching your research
  • Find out the new papers from selected authors
  • Updated daily for 49'000+ journals and 6000+ publishers
  • Define your Scifeed now

SciFeed Share & Cite This Article

MDPI and ACS Style

Chen, M.-C.; Hsu, W.-L.; Hwang, P.-A.; Chou, T.-C. Low Molecular Weight Fucoidan Inhibits Tumor Angiogenesis through Downregulation of HIF-1/VEGF Signaling under Hypoxia. Mar. Drugs 2015, 13, 4436-4451.

Show more citation formats Show less citations formats

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Mar. Drugs EISSN 1660-3397 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top