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Mar. Drugs 2015, 13(6), 3514-3530; doi:10.3390/md13063514

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

1
Department of Biotechnology, Dalian Medical University, Dalian 116044, China
2
College of Life Sciences, Liaoning Normal University, Dalian 116081, China
*
Authors to whom correspondence should be addressed.
Academic Editor: Paul Long
Received: 26 March 2015 / Accepted: 19 May 2015 / Published: 3 June 2015
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Abstract

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. View Full-Text
Keywords: fucoidan; lymphangiogenesis; hypoxia; HIF-1α; metastasis fucoidan; lymphangiogenesis; hypoxia; HIF-1α; metastasis
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).

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MDPI and ACS Style

Teng, H.; Yang, Y.; Wei, H.; Liu, Z.; Liu, Z.; Ma, Y.; Gao, Z.; Hou, L.; Zou, X. Fucoidan Suppresses Hypoxia-Induced Lymphangiogenesis and Lymphatic Metastasis in Mouse Hepatocarcinoma. Mar. Drugs 2015, 13, 3514-3530.

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