scholarly journals The Antitumor Effect of Gekko Sulfated Glycopeptide by Inhibiting bFGF-Induced Lymphangiogenesis

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Xiu-Li Ding ◽  
Ya-Nan Man ◽  
Jian Hao ◽  
Cui-Hong Zhu ◽  
Chang Liu ◽  
...  
Keyword(s):  
Immunohistochemical Staining ◽  
Antitumor Effect ◽  
Inhibitory Effect ◽  
Tube Formation ◽  
Fibroblast Growth ◽  
Lymphatic Endothelial Cells ◽  
Tumor Lymphangiogenesis ◽  
Extracellular Signal

Objective. To study the antilymphangiogenesis effect of Gekko Sulfated Glycopeptide (GSPP) on human lymphatic endothelial cells (hLECs).Methods. MTS was conducted to confirm the antiproliferation effect of GSPP on hLECs; flow cytometry was employed to detect hLECs cycle distribution; the antimigration effect of GSPP on hLECs was investigated by wound healing experiment and transwell experiment; tube formation assay was used to examine its inhibitory effect on the lymphangiogenesis; western blotting was conducted to detect the expression of extracellular signal-regulated kinase1/2 (Erk1/2) and p-Erk1/2 after GSPP and basic fibroblast growth factor (bFGF) treatment. Nude mice models were established to investigate the antitumor effect of GSPP in vivo. Decreased lymphangiogenesis caused by GSPP in vivo was verified by immunohistochemical staining.Results. In vitro, GSPP (10 μg/mL, 100 μg/mL) significantly inhibited bFGF-induced hLECs proliferation, migration, and tube-like structure formation (P<0.05) and antagonized the phosphorylation activation of Erk1/2 induced by bFGF. In vivo, GSPP treatment (200 mg/kg/d) not only inhibited the growth of colon carcinoma, but also inhibited the tumor lymphangiogenesis.Conclusion. GSPP possesses the antitumor ability by inhibiting bFGF-inducing lymphangiogenesis in vitro and in vivo, which may further inhibit tumor lymphatic metastasis.

scholarly journals Inhibitory Effect of Arctigenin from Fructus Arctii Extract on Melanin Synthesis via Repression of Tyrosinase Expression

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Hwayong Park ◽  
Kwang Hoon Song ◽  
Pil Mun Jung ◽  
Ji-Eun Kim ◽  
Hyunju Ro ◽  
...  
Keyword(s):  
Active Compound ◽  
Gene Promoter ◽  
Inhibitory Effect ◽  
Tyrosinase Activity ◽  
Dependent Manner ◽  
Melanin Content ◽  
Extracellular Signal Regulated Kinase ◽  
Extracellular Signal

To identify the active compound arctigenin in Fructus Arctii (dried seed of medicinal plantArctium lappa) and to elucidate the inhibitory mechanism in melanogenesis, we analyzed melanin content and tyrosinase activity on B16BL6 murine melanoma and melan-A cell cultures. Water extracts of Fructus Arctii were shown to inhibit tyrosinase activity in vitro and melanin content inα-melanocyte stimulating hormone-stimulated cells to similar levels as the well-known kojic acid and arbutin, respectively. The active compound arctigenin of Fructus Arctii displayed little or no cytotoxicity at all concentrations examined and decreased the relative melanin content and tyrosinase activity in a dose-dependent manner. Melanogenic inhibitory activity was also identified in vivo with zebrafish embryo. To determine the mechanism of inhibition, the effects of arctigenin on tyrosinase gene expression and tyrosinase promoter activity were examined. Also in addition, in the signaling cascade, arctigenin dose dependently decreased the cAMP level and promoted the phosphorylation of extracellular signal-regulated kinase. This result suggests that arctigenin downregulates cAMP and the tyrosinase enzyme through its gene promoter and subsequently upregulates extracellular signal-regulated kinase activity by increasing phosphorylation in the melanogenesis signaling pathway, which leads to a lower melanin content.

scholarly journals The microRNA miR-132 is a key regulator of lymphatic vascular remodelling

2021 ◽  
Author(s):  
Marc Achen ◽  
Valeria Arcucci ◽  
Musarat Ishaq ◽  
Sally Roufail ◽  
Kate Dredge ◽  
...  
Keyword(s):  
Growth Factors ◽  
Small Rna ◽  
Lymphatic Vessels ◽  
Tube Formation ◽  
Small Rna Sequencing ◽  
Lymphatic Endothelial Cells ◽  
Rna Molecules ◽  
Key Steps

Lymphangiogenesis (growth of new lymphatic vessels), and lymphatic remodelling more broadly, are important for disease progression in cancer, lymphedema and the pulmonary disease lymphangioleiomyomatosis. Multiple molecular pathways which signal for aspects of lymphangiogenesis are known but little is understood about their co-ordinate regulation in lymphatic endothelial cells (LECs). Small RNA molecules co-ordinately regulate complex biological processes, but knowledge about their involvement in lymphangiogenesis is limited. Here we used high-throughput small RNA sequencing of LECs to identify microRNAs (miRs) regulating lymphatic remodelling driven by the lymphangiogenic growth factors VEGF-C and VEGF-D. We identified miR-132 as up-regulated by both growth factors, and demonstrated that inhibiting miR-132 in LECs in vitro blocked cell proliferation and tube formation, key steps in lymphangiogenesis. We showed that miR-132 is expressed in human LECs in vivo in the lymphatics of human breast tumours expressing VEGF-D. Importantly, we demonstrated that inhibiting miR-132 in vivo blocked many aspects of lymphangiogenesis in mice. Finally, we identified mRNAs regulated by miR-132 in LECs, by sequencing after RNA-protein cross-linking and Argonaute immunoprecipitation, which demonstrated how miR-132 co-ordinately regulates signalling pathways in lymphangiogenesis. This study shows miR-132 is a critical regulator of lymphangiogenesis and a potential target for therapeutically manipulating lymphatic remodelling in disease.

scholarly journals WISP2 promotes cell proliferation via targeting ERK and YAP in ovarian cancer cells

2020 ◽  
Author(s):  
Zi-Qing Shi ◽  
Zi-Yan Chen ◽  
Yao Han ◽  
Heng-Yan Zhu ◽  
Meng-Dan Lyu ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
Inhibitory Effect ◽  
Ovarian Cancer Cells ◽  
Extracellular Signal ◽  
And Migration

Abstract Background: Wnt-inducible signaling pathway protein 2 (WISP2) is a wnt1-induced signaling pathway protein 2. Although studies indicate that WISP2 may promote the development of various tumors, its role in ovarian cancer remains unclear. The objective of the current study was to analyze the effects of WISP2 on the proliferation and migration of ovarian cancer cells in vitro and in vivo.Results: Immunohistochemistry and western blotting indicated that WISP2 was highly expressed in various ovarian cancer tissues and cell lines，but weakly expressed in normal ovary tissue. WISP2 deletion inhibited cell growth, clone formation, and migration of ovarian cancer cells while promoting cell apoptosis and affecting the cell cycle. This growth inhibitory effect caused by WISP2 loss is due to the inhibition of phosphorylated extracellular signal-related kinase (p-ERK)1/2, as well as CCAAT/enhancer-binding protein α (CEBPα) and CEPBβ. In addition, WISP2 deletion also activated the Yes-associated protein (YAP).Conclusion: WISP2 deletion inhibits ovarian cancer cell proliferation by affecting ERK signaling pathways.

scholarly journals Canstatin represses glioma growth by inhibiting formation of VM-like structures

2021 ◽  
Vol 12 (1) ◽  
pp. 309-319
Author(s):  
Yuqiang Ma ◽  
Tao Wu ◽  
Houjie Zhou ◽  
Guilu He ◽  
Yifei Li ◽  
...  
Keyword(s):  
Vasculogenic Mimicry ◽  
Angiogenesis Inhibitor ◽  
Inhibitory Effect ◽  
Protective Role ◽  
Tube Formation ◽  
Vascular Endothelial ◽  
Glioma Growth ◽  
Endothelial Growth Factor

Abstract Vasculogenic mimicry (VM) is different from classical tumor angiogenesis and does not depend on endothelial cells. VM is closely related to the prognosis of various cancers. Canstatin was first identified as an endogenous angiogenesis inhibitor. In the present study, the inhibitory effect of canstatin on VM formation was evaluated. Human glioblastoma cell lines U87 and U251 were letivirally transduced to overexpress canstatin gene or GFP as control. In vitro assays showed that canstatin overexpression reduced the tube formation of U87 and U251 cells in Matrigel. A xenograft glioma model was created by subcutaneous injection of lentivirally modified U87 cells into nude mice. The results of in vivo experiments showed that canstatin gene introduction inhibited the growth of glioma xenografts. In tumor xenografts overexpressing canstatin, U87-mediated formation of VM-like structures and VM-related VEGF (vascular endothelial growth factor) expression were remarkably reduced. Canstatin overexpression also decreased the phosphorylation of Akt and reduced the expression of Survivin in vitro. In addition, HIF-1α production and MMP-2 secretion were decreased by canstatin overexpression. Therefore, these results suggested a protective role of canstatin during VM-like structure formation of glioma probably via inhibiting signaling pathways inducing vasculogenic mimicry.

scholarly journals WISP2 promotes cell proliferation via targeting ERK and YAP in ovarian cancer cells

2020 ◽  
Author(s):  
Zi-Qing Shi ◽  
Zi-Yan Chen ◽  
Yao Han ◽  
Heng-Yan Zhu ◽  
Meng-Dan Lyu ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Inhibitory Effect ◽  
Ovarian Cancer Cells ◽  
Growth Inhibitory ◽  
Extracellular Signal ◽  
And Migration

Abstract Background Wnt inducible signaling protein 2 (WISP2) is a wnt1-induced signaling pathway protein 2. Although studies indicate that WISP2 may promote the development of various tumors, its role in ovarian cancer remains unclear. The objective of the current study was to analyze the effects of WISP2 on proliferation and migration of ovarian cancer cells in vitro and in vivo . Results Immunohistochemistry and western blot results indicated that WISP2 was highly expressed in various ovarian tissues and cell lines. WISP2 deletion inhibited cell growth, clone formation, and migration of ovarian cancer cells. WISP2 deletion promoted cell apoptosis and affected the cell cycle. This growth inhibitory effect caused by WISP2 loss is due to the inhibition of extracellular signal-related kinase (p-ERK)1/2, as well as CEBPα and CEBPβ. In addition, WISP2 deletion also activated the Yes-associated protein (YAP). Conclusion WISP2 deletion inhibits ovarian cancer cell proliferation by affecting ERK signaling pathways.

Abstract 198: Angiotensin II Inhibits Cardiac Angiogenesis via the Cooperation of p53 and Jagged 1

2012 ◽  
Vol 111 (suppl_1) ◽  
Author(s):  
Aili Guan ◽  
Hui Gong ◽  
Yong Ye ◽  
Jianguo Jia ◽  
Guoping Zhang ◽  
...  
Keyword(s):  
Hypoxia Inducible Factor ◽  
Underlying Mechanism ◽  
Inhibitory Effect ◽  
Tube Formation ◽  
Ang Ii ◽  
Capillary Formation ◽  
Angiogenic Effect ◽  
Endothelial Growth Factor

It is well established that angiotension II (Ang II) is an important regulator in vascular homeostasis. Under certain conditions, Ang II could exert anti-angiogenic effects in cardiovascular system. However, the potential mechanism is unclear. P53 has been reported to suppress angiogenesis by promoting hypoxia-inducible factor-1 (Hif-1α) degradation. This study was conducted to determine the contribution of P53 and the underlying mechanism to the anti-angiogenic effect of Ang II. Angiogenesis was determined by tube formation from the cardiac microvascular endothelial cells (ECs). Microvessel density and cardiac function were analyzed in mice subjected to Ang II infusion (200 ng/kg/min ) or vehicle for 2 weeks. Ang II (1μM) greatly inhibited tube formation and stimulated phosphorylation and upregulation of P53 in cultured cardiac ECs. P53 inhibitor, pifithrin-α (PFT-α,3.0mg/kg), significantly reversed the inhibitory effect of Ang II on tube formation. Vascular endothelial growth factor (VEGF ) and Hif-1α has been reported as important pro-angiogenetic factors. The present study indicated that Ang II decreased VEGF concentration in cultured medium and downregulated Hif-1α expression in cultured ECs. Interestingly, Ang II also stimulated the upregulation of Jagged 1, a ligand of Notch, but it didn't affect the Delta-like 4 (Dll 4) , another ligand of Notch, expression in cardiac ECs. However, PFT-α partly abolished these effects of Ang II. These results were consistent with the study in vivo. Further research revealed that siRNA-Jagged 1 transfection in cultured ECs dramatically abolished the phosphorylation of P53 and the downregulation of Hif-1α induced by Ang II. Additionally, Ang II- induced inhibitory effect on capillary formation was blocked by siRNA-Jagged 1 transfection in cultured cardiac ECs. In conclusion, Ang II promoted the phosphorylation and upregulation of P53, and increased Jagged 1 expression, the upregulation of Jagged 1 in turn stimulated the phosphorylation of P53, which resulted in the downregulation of Hif-1α and VEGF, then induced the inhibitory effects of Ang II on capillary formation. The present data suggest that Ang II exerts anti-angiogenesis via the cooperation of P53 and Jagged 1 in vitro and in vivo.

scholarly journals Vaccinium myrtillus(Bilberry) Extracts Reduce AngiogenesisIn VitroandIn Vivo

2010 ◽  
Vol 7 (1) ◽  
pp. 47-56 ◽  
Author(s):  
Nozomu Matsunaga ◽  
Yuichi Chikaraishi ◽  
Masamitsu Shimazawa ◽  
Shigeru Yokota ◽  
Hideaki Hara
Keyword(s):  
Protein Kinase ◽  
Umbilical Vein ◽  
Tube Formation ◽  
Vaccinium Myrtillus ◽  
Oxygen Induced Retinopathy ◽  
Extracellular Signal ◽  
And Migration ◽  
Umbilical Vein Endothelial Cells

Vaccinium myrtillus(Bilberry) extracts (VME) were tested for effects on angiogenesisin vitroandin vivo. VME (0.3–30 µg ml−1) and GM6001 (0.1–100 µM; a matrix metalloproteinase inhibitor) concentration-dependently inhibited both tube formation and migration of human umbilical vein endothelial cells (HUVECs) induced by vascular endothelial growth factor-A (VEGF-A). In addition, VME inhibited VEGF-A-induced proliferation of HUVECs. VME inhibited VEGF-A-induced phosphorylations of extracellular signal-regulated kinase 1/2 (ERK 1/2) and serine/threonine protein kinase family protein kinase B (Akt), but not that of phospholipase Cγ (PLCγ). In anin vivoassay, intravitreal administration of VME inhibited the formation of neovascular tufts during oxygen-induced retinopathy in mice. Thus, VME inhibited angiogenesis bothin vitroandin vivo, presumably by inhibiting the phosphorylations of ERK 1/2 and Akt. These findings indicate that VME may be effective against retinal diseases involving angiogenesis, providing it can reach the retina after its administration. Further investigations will be needed to clarify the major angiogenesis-modulating constituent(s) of VME.

Syndecan-1 up-regulated by ephrinB2/EphB4 plays dual roles in inflammatory angiogenesis

Blood ◽  
2004 ◽  
Vol 104 (4) ◽  
pp. 1025-1033 ◽  
Author(s):  
Kuo Yuan ◽  
Tse-Ming Hong ◽  
Jeremy J. W. Chen ◽  
Wan Hua Tsai ◽  
Ming T. Lin
Keyword(s):  
Endothelial Cells ◽  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Growth Factor Receptor ◽  
Inhibitory Effect ◽  
Fibroblast Growth ◽  
Downstream Effects ◽  
Inflammatory Angiogenesis

AbstractEphrinB2 and EphB4, its cognate receptor, are important in the vascular development of the mouse embryo. Their roles in human inflammatory angiogenesis, however, are not well understood. By examining hyperinflammatory lesions, we saw that ephrinB2 was predominantly expressed in macrophage-like cells and EphB4 in small venules. Because macrophages usually transmigrate through postcapillary venules during inflammation, we wanted to explore the downstream effects of EphB4 after binding to ephrinB2. By using cDNA microarray technique and following reverse transcriptase–polymerase chain reaction (RT-PCR), we found that syntenin and syndecan-1 were up-regulated in EphB4-positive endothelial cells dose dependently and time dependently after stimulation with preclustered ephrinB2. In vitro, ephrinB2 suppressed the angiogenic effects of basic fibroblast growth factor (bFGF) on EphB4-positive endothelial cells, partially due to syndecan-1's competition with fibroblast growth factor receptor (FGFR) for bFGF. However, ephrinB2 exhibited angiogenic effects in vivo, possibly due to an inflammation-associated enzyme—heparanase. The enzymes could convert the inhibitory effect of ephrinB2 on EphB4-positive endothelial cells to an activating effect by removing poorly sulfated side chains of up-regulated syndecan-1 ectodomain. Depending on the presence of heparanases, the roles of syndecan-1 may be opposite in different physiological settings.

scholarly journals Inhibitory Effect of Isoliquiritin, a Compound in Licorice Root, on Angiogenesis in Vivo and Tube Formation in Vitro.

1995 ◽  
Vol 18 (10) ◽  
pp. 1382-1386 ◽  
Author(s):  
Shinjiro KOBAYASHI ◽  
Takayuki MIYAMOTO ◽  
Ikuko KIMURA ◽  
Masayasu KIMURA
Keyword(s):  
Inhibitory Effect ◽  
Tube Formation ◽  
Licorice Root

scholarly journals Platelet interaction with lymphatics aggravates intestinal inflammation by suppressing lymphangiogenesis

2016 ◽  
Vol 311 (2) ◽  
pp. G276-G285 ◽  
Author(s):  
Hirokazu Sato ◽  
Masaaki Higashiyama ◽  
Hideaki Hozumi ◽  
Shingo Sato ◽  
Hirotaka Furuhashi ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Mouse Model ◽  
Intestinal Inflammation ◽  
Inflammatory Cells ◽  
Inhibitory Effect ◽  
Vegf Receptor ◽  
Lymphatic Endothelial Cells ◽  
Antiplatelet Antibody

Lymphatic failure is a histopathological feature of inflammatory bowel disease (IBD). Recent studies show that interaction between platelets and podoplanin on lymphatic endothelial cells (LECs) suppresses lymphangiogenesis. We aimed to investigate the role of platelets in the inflammatory process of colitis, which is likely to be through modulation of lymphangiogenesis. Lymphangiogenesis in colonic mucosal specimens from patients with IBD was investigated by studying mRNA expression of lymphangiogenic factors and histologically by examining lymphatic vessel (LV) densities. Involvement of lymphangiogenesis in intestinal inflammation was studied by administering VEGF-receptor 3 (VEGF-R3) inhibitors to the mouse model of colitis using dextran sulfate sodium and evaluating platelet migration to LVs. The inhibitory effect of platelets on lymphangiogenesis was investigated in vivo by administering antiplatelet antibody to the colitis mouse model and in vitro by coculturing platelets with lymphatic endothelial cells. Although mRNA expressions of lymphangiogenic factors such as VEGF-R3 and podoplanin were significantly increased in the inflamed mucosa of patients with IBD compared with those with quiescent mucosa, there was no difference in LV density between them. In the colitis model, VEGF-R3 inhibition resulted in aggravated colitis, decreased lymphatic density, and increased platelet migration to LVs. Administration of an antiplatelet antibody increased LV densities and significantly ameliorated colitis. Coculture with platelets inhibited proliferation of LECs in vitro. Our data suggest that despite elevated lymphangiogenic factors during colonic inflammation, platelet migration to LVs resulted in suppressed lymphangiogenesis, leading to aggravation of colitis by blocking the clearance of inflammatory cells. Modulating the interaction between platelets and LVs could be a new therapeutic means for treating IBD.

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