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Fucoidan Suppresses Hypoxia-Induced Lymphangiogenesis and Lymphatic Metastasis in Mouse Hepatocarcinoma

Metastasis, the greatest clinical challenge associated with cancer, is closely connected to multiple biological processes, including invasion and adhesion. The hypoxic environment in tumors is an important factor that causes tumor metastasis by activating HIF-1α. Fucoidan, extracted from brown algae...

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Autores principales: Teng, Hongming, Yang, Yazong, Wei, Hengyun, Liu, Zundong, Liu, Zhichao, Ma, Yanhong, Gao, Zixiang, Hou, Lin, Zou, Xiangyang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4483642/
https://www.ncbi.nlm.nih.gov/pubmed/26047481
http://dx.doi.org/10.3390/md13063514
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author Teng, Hongming
Yang, Yazong
Wei, Hengyun
Liu, Zundong
Liu, Zhichao
Ma, Yanhong
Gao, Zixiang
Hou, Lin
Zou, Xiangyang
author_facet Teng, Hongming
Yang, Yazong
Wei, Hengyun
Liu, Zundong
Liu, Zhichao
Ma, Yanhong
Gao, Zixiang
Hou, Lin
Zou, Xiangyang
author_sort Teng, Hongming
collection PubMed
description Metastasis, the greatest clinical challenge associated with cancer, is closely connected to multiple biological processes, including invasion and adhesion. The hypoxic environment in tumors is an important factor that causes tumor metastasis by activating HIF-1α. Fucoidan, extracted from brown algae, is a sulfated polysaccharide and, as a novel marine biological material, has been used to treat various disorders in China, Korea, Japan and other countries. In the present study, we demonstrated that fucoidan derived from Undaria pinnatifida sporophylls significantly inhibits the hypoxia-induced expression, nuclear translocation and activity of HIF-1α, the synthesis and secretion of VEGF-C and HGF, cell invasion and lymphatic metastasis in a mouse hepatocarcinoma Hca-F cell line. Fucoidan also suppressed lymphangiogenesis in vitro and in vivo. In addition, accompanied by a reduction in the HIF-1α nuclear translocation and activity, fucoidan significantly reduced the levels of p-PI3K, p-Akt, p-mTOR, p-ERK, NF-κB, MMP-2 and MMP-9, but increased TIMP-1 levels. These results indicate strongly that the anti-metastasis and anti-lymphangiogenesis activities of fucoidan are mediated by suppressing HIF-1α/VEGF-C, which attenuates the PI3K/Akt/mTOR signaling pathways.
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spelling pubmed-44836422015-06-30 Fucoidan Suppresses Hypoxia-Induced Lymphangiogenesis and Lymphatic Metastasis in Mouse Hepatocarcinoma Teng, Hongming Yang, Yazong Wei, Hengyun Liu, Zundong Liu, Zhichao Ma, Yanhong Gao, Zixiang Hou, Lin Zou, Xiangyang Mar Drugs Article Metastasis, the greatest clinical challenge associated with cancer, is closely connected to multiple biological processes, including invasion and adhesion. The hypoxic environment in tumors is an important factor that causes tumor metastasis by activating HIF-1α. Fucoidan, extracted from brown algae, is a sulfated polysaccharide and, as a novel marine biological material, has been used to treat various disorders in China, Korea, Japan and other countries. In the present study, we demonstrated that fucoidan derived from Undaria pinnatifida sporophylls significantly inhibits the hypoxia-induced expression, nuclear translocation and activity of HIF-1α, the synthesis and secretion of VEGF-C and HGF, cell invasion and lymphatic metastasis in a mouse hepatocarcinoma Hca-F cell line. Fucoidan also suppressed lymphangiogenesis in vitro and in vivo. In addition, accompanied by a reduction in the HIF-1α nuclear translocation and activity, fucoidan significantly reduced the levels of p-PI3K, p-Akt, p-mTOR, p-ERK, NF-κB, MMP-2 and MMP-9, but increased TIMP-1 levels. These results indicate strongly that the anti-metastasis and anti-lymphangiogenesis activities of fucoidan are mediated by suppressing HIF-1α/VEGF-C, which attenuates the PI3K/Akt/mTOR signaling pathways. MDPI 2015-06-03 /pmc/articles/PMC4483642/ /pubmed/26047481 http://dx.doi.org/10.3390/md13063514 Text en © 2015 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Teng, Hongming
Yang, Yazong
Wei, Hengyun
Liu, Zundong
Liu, Zhichao
Ma, Yanhong
Gao, Zixiang
Hou, Lin
Zou, Xiangyang
Fucoidan Suppresses Hypoxia-Induced Lymphangiogenesis and Lymphatic Metastasis in Mouse Hepatocarcinoma
title Fucoidan Suppresses Hypoxia-Induced Lymphangiogenesis and Lymphatic Metastasis in Mouse Hepatocarcinoma
title_full Fucoidan Suppresses Hypoxia-Induced Lymphangiogenesis and Lymphatic Metastasis in Mouse Hepatocarcinoma
title_fullStr Fucoidan Suppresses Hypoxia-Induced Lymphangiogenesis and Lymphatic Metastasis in Mouse Hepatocarcinoma
title_full_unstemmed Fucoidan Suppresses Hypoxia-Induced Lymphangiogenesis and Lymphatic Metastasis in Mouse Hepatocarcinoma
title_short Fucoidan Suppresses Hypoxia-Induced Lymphangiogenesis and Lymphatic Metastasis in Mouse Hepatocarcinoma
title_sort fucoidan suppresses hypoxia-induced lymphangiogenesis and lymphatic metastasis in mouse hepatocarcinoma
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4483642/
https://www.ncbi.nlm.nih.gov/pubmed/26047481
http://dx.doi.org/10.3390/md13063514
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