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

Marine drugs, 2015-07, Vol.13 (7), p.4436-4451 [Peer Reviewed Journal]

Copyright MDPI AG 2015 ;2015 by the authors; licensee MDPI, Basel, Switzerland. 2015 ;ISSN: 1660-3397 ;EISSN: 1660-3397 ;DOI: 10.3390/md13074436 ;PMID: 26193287

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Title:
Low Molecular Weight Fucoidan Inhibits Tumor Angiogenesis through Downregulation of HIF-1/VEGF Signaling under Hypoxia
Author: Chen, Meng-Chuan ; Hsu, Wen-Lin ; Hwang, Pai-An ; Chou, Tz-Chong
Subjects: angiogenesis ; Antineoplastic Agents - pharmacology ; bladder cancer ; Cell Line, Tumor ; Down-Regulation - drug effects ; Humans ; Hypoxia - metabolism ; Hypoxia-Inducible Factor 1 - antagonists & inhibitors ; Hypoxia-Inducible Factor 1 - physiology ; hypoxia-inducible factor 1 alpha ; Hypoxia-Inducible Factor 1, alpha Subunit - antagonists & inhibitors ; Hypoxia-Inducible Factor 1, alpha Subunit - physiology ; low molecular weight fucoidan ; Neovascularization, Pathologic - drug therapy ; Polysaccharides - pharmacology ; Signal Transduction - drug effects ; Signal Transduction - physiology ; Urinary Bladder Neoplasms - blood supply ; Urinary Bladder Neoplasms - drug therapy ; vascular endothelial growth factor ; Vascular Endothelial Growth Factor A - antagonists & inhibitors ; Vascular Endothelial Growth Factor A - physiology
Is Part Of: Marine drugs, 2015-07, Vol.13 (7), p.4436-4451
Description: 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.
Publisher: Switzerland: MDPI AG
Language: English
Identifier: ISSN: 1660-3397
EISSN: 1660-3397
DOI: 10.3390/md13074436
PMID: 26193287
Source: Geneva Foundation Free Medical Journals at publisher websites
MEDLINE
PubMed Central
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ProQuest Central
DOAJ Directory of Open Access Journals

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

Copyright MDPI AG 2015 ;2015 by the authors; licensee MDPI, Basel, Switzerland. 2015 ;ISSN: 1660-3397 ;EISSN: 1660-3397 ;DOI: 10.3390/md13074436 ;PMID: 26193287

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