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

Teng H, Yang Y, Wei H, Liu Z, Liu Z, Ma Y, Gao Z, Hou L, Zou X - Mar Drugs (2015)

Bottom Line: Metastasis, the greatest clinical challenge associated with cancer, is closely connected to multiple biological processes, including invasion and adhesion.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 Article: PubMed Central - PubMed

Affiliation: Department of Biotechnology, Dalian Medical University, Dalian 116044, China. thm0529@126.com.

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.

No MeSH data available.


Related in: MedlinePlus

Effect of fucoidan on the activation of hypoxia-related signaling pathways. The levels of p-PI3K, p-AKT, p-mTOR, p-ERK and NF-κB were decreased, which indicated that the activation of PI3K/AKT/mTOR, ERK and NF-κB in CoCl2-treated cells was downregulated. Each value represents the mean ± SD. #p < 0.05, ##p < 0.01, compared with the control. * p < 0.05, ** p < 0.01, compared with the CoCl2 group.
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marinedrugs-13-03514-f006: Effect of fucoidan on the activation of hypoxia-related signaling pathways. The levels of p-PI3K, p-AKT, p-mTOR, p-ERK and NF-κB were decreased, which indicated that the activation of PI3K/AKT/mTOR, ERK and NF-κB in CoCl2-treated cells was downregulated. Each value represents the mean ± SD. #p < 0.05, ##p < 0.01, compared with the control. * p < 0.05, ** p < 0.01, compared with the CoCl2 group.

Mentions: To characterize the mechanism of the inhibitory effect of fucoidan on Hca-F cells under hypoxia conditions, the activities of the PI3K/Akt/mTOR, ERK and NF-κB signaling pathways were assessed. Western blot analysis showed that p-PI3K, p-AKT, p-mTOR, p-ERK and NF-κB protein levels were downregulated in Hca-F cells treated with fucoidan under hypoxia conditions (Figure 6).


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

Teng H, Yang Y, Wei H, Liu Z, Liu Z, Ma Y, Gao Z, Hou L, Zou X - Mar Drugs (2015)

Effect of fucoidan on the activation of hypoxia-related signaling pathways. The levels of p-PI3K, p-AKT, p-mTOR, p-ERK and NF-κB were decreased, which indicated that the activation of PI3K/AKT/mTOR, ERK and NF-κB in CoCl2-treated cells was downregulated. Each value represents the mean ± SD. #p < 0.05, ##p < 0.01, compared with the control. * p < 0.05, ** p < 0.01, compared with the CoCl2 group.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4483642&req=5

marinedrugs-13-03514-f006: Effect of fucoidan on the activation of hypoxia-related signaling pathways. The levels of p-PI3K, p-AKT, p-mTOR, p-ERK and NF-κB were decreased, which indicated that the activation of PI3K/AKT/mTOR, ERK and NF-κB in CoCl2-treated cells was downregulated. Each value represents the mean ± SD. #p < 0.05, ##p < 0.01, compared with the control. * p < 0.05, ** p < 0.01, compared with the CoCl2 group.
Mentions: To characterize the mechanism of the inhibitory effect of fucoidan on Hca-F cells under hypoxia conditions, the activities of the PI3K/Akt/mTOR, ERK and NF-κB signaling pathways were assessed. Western blot analysis showed that p-PI3K, p-AKT, p-mTOR, p-ERK and NF-κB protein levels were downregulated in Hca-F cells treated with fucoidan under hypoxia conditions (Figure 6).

Bottom Line: Metastasis, the greatest clinical challenge associated with cancer, is closely connected to multiple biological processes, including invasion and adhesion.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 Article: PubMed Central - PubMed

Affiliation: Department of Biotechnology, Dalian Medical University, Dalian 116044, China. thm0529@126.com.

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.

No MeSH data available.


Related in: MedlinePlus