Sulfated fucoidan FP08S2 inhibits lung cancer cell growth in vivo by disrupting angiogenesis via targeting VEGFR2/VEGF and blocking VEGFR2/Erk/VEGF signaling.

Publisher: Elsevier Science Ireland Country of Publication: Ireland NLM ID: 7600053 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1872-7980 (Electronic) Linking ISSN: 03043835 NLM ISO Abbreviation: Cancer Lett Subsets: MEDLINE

Publication: Limerick : Elsevier Science Ireland
Original Publication: Amsterdam, Elsevier/North-Holland.

Neovascularization, Pathologic*; Angiogenesis Inhibitors/*pharmacology ; Cell Proliferation/*drug effects ; Extracellular Signal-Regulated MAP Kinases/*metabolism ; Lung Neoplasms/*drug therapy ; Polysaccharides/*pharmacology ; Signal Transduction/*drug effects ; Vascular Endothelial Growth Factor A/*antagonists & inhibitors ; Vascular Endothelial Growth Factor Receptor-2/*antagonists & inhibitors; A549 Cells ; Animals ; Cell Movement/drug effects ; Chick Embryo ; Chorioallantoic Membrane/blood supply ; Dose-Response Relationship, Drug ; Human Umbilical Vein Endothelial Cells/drug effects ; Human Umbilical Vein Endothelial Cells/metabolism ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism ; Lung Neoplasms/blood supply ; Lung Neoplasms/metabolism ; Lung Neoplasms/pathology ; Mice, Inbred BALB C ; Mice, Nude ; Neoplasm Invasiveness ; Neovascularization, Physiologic/drug effects ; Time Factors ; Tumor Burden/drug effects ; Vascular Endothelial Growth Factor A/metabolism ; Vascular Endothelial Growth Factor Receptor-2/metabolism ; Xenograft Model Antitumor Assays

Fucoidan may inhibit angiogenesis. However, its functional target molecule and the underlying mechanism are still vague. In the present study, we showed that sulfated fucoidan FP08S2 from Sargassum fusiforme inhibited tube formation as well as migration and invasion of human microvascular endothelial cells (HMEC-1). In addition, FP08S2 was confirmed to disrupt VEGF-induced angiogenesis both in vitro and in vivo. Further study indicated that FP08S2 could bind to both VEGF and VEGFR2 to interfere with VEGF-VEGFR2 interaction. Moreover, VEGFR2/Erk/VEGF signaling pathway was blocked by FP08S2 in HMEC-1 cells. Importantly, FP08S2 impeded the growth and microvessel formation of A549 cancer cell xenograft in nude mice. These results suggested that FP08S2 presented remarkable anti-angiogenic activity via blocking VEGF signaling and could be a potential novel leading compound to inhibit lung cancer cell growth.
(Copyright © 2016. Published by Elsevier Ireland Ltd.)

Keywords: Angiogenesis; Fucoidan; Lung cancer; VEGF

0 (Angiogenesis Inhibitors)
0 (HIF1A protein, human)
0 (Hypoxia-Inducible Factor 1, alpha Subunit)
0 (Polysaccharides)
0 (VEGFA protein, human)
0 (Vascular Endothelial Growth Factor A)
9072-19-9 (fucoidan)
EC 2.7.10.1 (KDR protein, human)
EC 2.7.10.1 (Vascular Endothelial Growth Factor Receptor-2)
EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)

Date Created: 20160830 Date Completed: 20170728 Latest Revision: 20240109

20250114

10.1016/j.canlet.2016.08.020

27569654