TY - JOUR
T1 - Fucoidan from Laminaria japonica exerts antitumor effects on angiogenesis and micrometastasis in triple-negative breast cancer cells
AU - Hsu, Wen Jing
AU - Lin, Mei Hsiang
AU - Kuo, Tai Chih
AU - Chou, Chih Ming
AU - Mi, Fwu Long
AU - Cheng, Chia Hsiung
AU - Lin, Cheng Wei
N1 - Copyright © 2020 Elsevier B.V. All rights reserved.
PY - 2020/4/15
Y1 - 2020/4/15
N2 - Fucoidan is a fucose-rich polysaccharide that has gained attention for its various anticancer properties. However, the effect and underlying mechanism of fucoidan on triple-negative breast cancer (TNBC) are still unknown. Herein, we investigated the anticancer potential of fucoidan from Laminaria japonica. We found that fucoidan showed modest antiproliferative activity against TNBC cells, while it effectively reduced migratory and invasive capacities. Mechanistically, fucoidan suppressed activation of MAPK and PI3K followed by inhibition of AP-1 and NF-κB signaling in TNBC. Additionally, fucoidan downregulated expressions of proangiogenic factors in TNBC cells, and fucoidan blocked tumor-elicited tube formation by human umbilical vascular endothelial cells (HUVECs). We also observed that fucoidan blocked tumor adhesion and invasion towards HUVECs. Surprisingly, fucoidan robustly suppressed tube formation on HUVECs. Moreover, fucoidan inhibited in vivo angiogenesis and micrometastasis in a transgenic zebrafish model. Together, L. japonica fucoidan exhibits potent antitumor effects by its attenuation of invasiveness and proangiogenesis in TNBC.
AB - Fucoidan is a fucose-rich polysaccharide that has gained attention for its various anticancer properties. However, the effect and underlying mechanism of fucoidan on triple-negative breast cancer (TNBC) are still unknown. Herein, we investigated the anticancer potential of fucoidan from Laminaria japonica. We found that fucoidan showed modest antiproliferative activity against TNBC cells, while it effectively reduced migratory and invasive capacities. Mechanistically, fucoidan suppressed activation of MAPK and PI3K followed by inhibition of AP-1 and NF-κB signaling in TNBC. Additionally, fucoidan downregulated expressions of proangiogenic factors in TNBC cells, and fucoidan blocked tumor-elicited tube formation by human umbilical vascular endothelial cells (HUVECs). We also observed that fucoidan blocked tumor adhesion and invasion towards HUVECs. Surprisingly, fucoidan robustly suppressed tube formation on HUVECs. Moreover, fucoidan inhibited in vivo angiogenesis and micrometastasis in a transgenic zebrafish model. Together, L. japonica fucoidan exhibits potent antitumor effects by its attenuation of invasiveness and proangiogenesis in TNBC.
KW - Apoptosis/drug effects
KW - Cell Line, Tumor
KW - Cell Proliferation/drug effects
KW - Female
KW - Gene Expression Regulation, Neoplastic/drug effects
KW - Humans
KW - Laminaria/chemistry
KW - Mitogen-Activated Protein Kinase Kinases/genetics
KW - NF-kappa B/genetics
KW - Neoplasm Micrometastasis
KW - Neovascularization, Pathologic/drug therapy
KW - Polysaccharides/chemistry
KW - Signal Transduction/drug effects
KW - Transcription Factor AP-1/genetics
KW - Triple Negative Breast Neoplasms/drug therapy
KW - Xenograft Model Antitumor Assays
UR - http://www.scopus.com/inward/record.url?scp=85078731130&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85078731130&partnerID=8YFLogxK
U2 - 10.1016/j.ijbiomac.2020.01.256
DO - 10.1016/j.ijbiomac.2020.01.256
M3 - Article
C2 - 32004612
AN - SCOPUS:85078731130
SN - 0141-8130
VL - 149
SP - 600
EP - 608
JO - International Journal of Biological Macromolecules
JF - International Journal of Biological Macromolecules
ER -