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

Chen, Huanjun; Cong, Qifei; Du, Zhaohui; Liao, Weiqi; Zhang, Lei; Yao, Yanli; Ding, Kan

doi:10.1016/j.canlet.2016.08.020

Cited by 85 publications

(69 citation statements)

References 40 publications

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“…It contains substantial percentages of l ‐fucose and sulfate ester groups (Bilan et al, ). Fucoidan exhibits a wide variety of biological activities, including anticoagulant (Mourao, ), anti‐inflammatory (Li & Ye, ) and anticancer activities (Chen et al, ). Regarding osteogenesis, several studies have reported that fucoidan affects osteoblast differentiation in osteoblast‐like cells (MG‐63 cells), adipose‐derived stem cells (Park, Lee, Lim, & Lee, ) and human alveolar bone marrow mesenchymal stem cells (Kim et al, ).…”

Section: Introductionmentioning

confidence: 99%

Fucoidan‐induced osteogenic differentiation promotes angiogenesis by inducing vascular endothelial growth factor secretion and accelerates bone repair

Kim

Yang

You

et al. 2017

J Tissue Eng Regen Med

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Osteogenesis and angiogenesis, including cell-cell communication between blood vessel cells and bone cells, are essential for bone repair. Fucoidan is a chemical compound that has a variety of biological activities. It stimulates osteoblast differentiation in human mesenchymal stem cells (MSCs), which in turn induces angiogenesis. However, the mechanism by which this communication between osteoblasts and endothelial cells is mediated remains unclear. Thus, the aim of this study was to clarify the relationship between fucoidan-induced osteoblastic differentiation in MSCs and angiogenesis in endothelial cells. First, the effect was confirmed of fucoidan on osteoblast differentiation in MSCs and obtained conditioned media from these cells (Fucoidan-MSC-CM). Next, the angiogenic activity of Fucoidan-MSC-CM was investigated and it was found that it stimulated angiogenesis, demonstrated by proliferation, tube formation, migration and sprout capillary formation in human umbilical vein endothelial cells. Messenger ribonucleic acid expression and protein secretion of vascular endothelial growth factor (VEGF) were dramatically increased during fucoidan-induced osteoblast differentiation and that its angiogenic activities were reduced by a VEGF/VEGF receptor-specific binding inhibitor. Furthermore, Fucoidan-MSC-CM increased the phosphorylation of mitogen-activated protein kinase and PI3K/AKT/eNOS signalling pathway, and that its angiogenic effects were markedly suppressed by SB203580 and AKT 1/2 inhibitor. Finally, an in vivo study was conducted and it was found that fucoidan accelerated new blood vessel formation and partially promoted bone formation in a rabbit model of a calvarial bone defect. This is the first study to investigate the angiogenic effect of fucoidan-induced osteoblastic differentiation through VEGF secretion, suggesting the therapeutic potential of fucoidan for enhancing bone repair.

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Section: Introductionmentioning

confidence: 99%

Fucoidan‐induced osteogenic differentiation promotes angiogenesis by inducing vascular endothelial growth factor secretion and accelerates bone repair

Kim

Yang

You

et al. 2017

J Tissue Eng Regen Med

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“…Researchers have found multiple signaling pathways which are linked to lung cancer. These include the PI3K-AKT [17 -19], VEGF [20][21][22], and P53 [23][24][25] signaling pathways. There is agreement with the fact that PTEN is a dual protein/lipid phosphatase.…”

Section: Discussionmentioning

confidence: 99%

Inhibitory effect of platinum (II) complex of curcumin on non-small cell lung cancer via the PI3K-AKT pathway

Wang¹,

Li²

2018

Trop. J. Pharm Res

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Purpose: To study the effect of platinum (II) complex of curcumin (PCC) on non-small cell lung cancer (NSCLC) using human NSCLC cell line A549. Methods: The anti-proliferative and apoptotic effects of PCC against NSCLC were investigated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), Annexin V-FITC/propidium iodide double staining, quantitative real-time polymerase chain reaction (qRT-PCR), and western blot assays. Results: First, MTT assay and Annexin V-FITC/propidium iodide double staining results revealed that PCC possesses strong anti-cancer potency and high safety, when compared with cisplatin. Western blotting and qRT-PCR results showed that PCC inhibited the viability of NSCLC cells, decreased the expressions of PI3K, VEGF, AKT and Bcl-2, and upregulated the expression of PTEN. Conclusion: These results indicate that PCC promotes apoptosis in A549 cells via PTEN/PI3K/AKT signaling pathways.

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“…The SPR experiment was carried out as previous report [27]. Briefly, proteins (VEGF or VEGFR2) were immobilized on a CM5 sensor chip by the amine coupling method [28].…”

Section: Methodsmentioning

confidence: 99%

Structural Determinant and Its Underlying Molecular Mechanism of STPC2 Related to Anti-Angiogenic Activity

Cui

et al. 2017

Marine Drugs

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In this study, we aimed to use different strategies to further uncover the anti-angiogenic molecular mechanism of a fucoidan-like polysaccharide STPC2, isolated from brown alga Sargassum thunbergii. A desulfated derivative, STPC2-DeS, was successfully prepared and identified. The native polysaccharide and desulfated product were subjected to evaluate their anti-angiogenic effects. In the tube formation assay, STPC2 showed dose-dependent inhibition. In addition, STPC2 could distinctly inhibit the permeation of HUVEC cells into the lower chamber. Moreover, a significant reduction of microvessel density was observed in chick chorioallantoic membrane assay treated with STPC2. Meanwhile, STPC2 was found to repress the VEGF-induced neovessel formation in the matrigel plug assay in vivo. However, STPC2-DeS failed to suppress the anti-angiogenic activity via these in vitro and in vivo strategies. In addition, we demonstrated that STPC2 could significantly downregulate the phosphorylation of VEGFR2 and its related downstream Src family kinase, focal adhesion kinase, and AKT kinase. Furthermore, surface plasmon resonance assay revealed that STPC2 bound strongly to VEGF to interfere with VEGF–VEGFR2 interaction. Taken together, these results evidently demonstrated that STPC2 exhibited a potent anti-angiogenic activity through binding to VEGF via sulfated groups to impede VEGF–VEGFR2 interaction, thus affected the downstream signaling molecules.

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

Cited by 85 publications

References 40 publications

Fucoidan‐induced osteogenic differentiation promotes angiogenesis by inducing vascular endothelial growth factor secretion and accelerates bone repair

Fucoidan‐induced osteogenic differentiation promotes angiogenesis by inducing vascular endothelial growth factor secretion and accelerates bone repair

Inhibitory effect of platinum (II) complex of curcumin on non-small cell lung cancer via the PI3K-AKT pathway

Structural Determinant and Its Underlying Molecular Mechanism of STPC2 Related to Anti-Angiogenic Activity

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