scholarly journals Phytochemicals Targeting VEGF and VEGF-Related Multifactors as Anticancer Therapy

2019 ◽  
Vol 8 (3) ◽  
pp. 350 ◽  
Author(s):  
Amna Parveen ◽  
Lalita Subedi ◽  
Heung Kim ◽  
Zahra Khan ◽  
Zahra Zahra ◽  
...  
Keyword(s):  
Tyrosine Kinases ◽  
Anticancer Therapy ◽  
Cancer Growth ◽  
Vascular Endothelial ◽  
Vegf Signaling ◽  
Multiple Factors ◽  
Cancer Initiation ◽  
Bioactive Phytochemicals ◽  
Endothelial Growth Factor

The role of vascular endothelial growth factor (VEGF) in cancer cells is not limited to angiogenesis; there are also multiple factors, such as neuropilins (non-tyrosine kinases receptors), tyrosine kinases receptors, immunodeficiencies, and integrins, that interact with VEGF signaling and cause cancer initiation. By combating these factors, tumor progression can be inhibited or limited. Natural products are sources of several bioactive phytochemicals that can interact with VEGF-promoting factors and inhibit them through various signaling pathways, thereby inhibiting cancer growth. This review provides a deeper understanding of the relation and interaction of VEGF with cancer-promoting factors and phytochemicals in order to develop multi-targeted cancer prevention and treatment.

scholarly journals Zebrafish G protein γ2 is required for VEGF signaling during angiogenesis

Blood ◽  
2006 ◽  
Vol 108 (1) ◽  
pp. 160-166 ◽  
Author(s):  
TinChung Leung ◽  
Hui Chen ◽  
Anna M. Stauffer ◽  
Kathryn E. Giger ◽  
Soniya Sinha ◽  
...  
Keyword(s):  
Blood Vessels ◽  
G Protein ◽  
Tyrosine Kinases ◽  
Vascular Endothelial ◽  
Breast Cancers ◽  
Serine Threonine Kinase ◽  
Threonine Kinase ◽  
Vegf Signaling ◽  
Promising Treatment ◽  
Endothelial Growth Factor

Vascular endothelial growth factor (VEGF) is a major mediator of pathologic angiogenesis, a process necessary for the formation of new blood vessels to support tumor growth. Historically, VEGF has been thought to signal via receptor tyrosine kinases, which are not typically considered to be G protein dependent. Here, we show that targeted knockdown of the G protein gng2 gene (Gγ2) blocks the normal angiogenic process in developing zebrafish embryos. Moreover, loss of gng2 function inhibits the ability of VEGF to promote the angiogenic sprouting of blood vessels by attenuating VEGF induced phosphorylation of phospholipase C-gamma1 (PLCγ1) and serine/threonine kinase (AKT). Collectively, these results demonstrate a novel interaction between Gγ2- and VEGF-dependent pathways to regulate the angiogenic process in a whole-animal model. Blocking VEGF function using a humanized anti-VEGF antibody has emerged as a promising treatment for colorectal, non-small lung cell, and breast cancers. However, this treatment may cause considerable side effects. Our findings provide a new opportunity for cotargeting G protein- and VEGF-dependent pathways to synergistically block pathologic angiogenesis, which may lead to a safer and more efficacious therapeutic regimen to fight cancer. (Blood. 2006;108:160-166)

scholarly journals Rap1 promotes VEGFR2 activation and angiogenesis by a mechanism involving integrin αvβ3

Blood ◽  
2011 ◽  
Vol 118 (7) ◽  
pp. 2015-2026 ◽  
Author(s):  
Sribalaji Lakshmikanthan ◽  
Magdalena Sobczak ◽  
Changzoon Chun ◽  
Angela Henschel ◽  
Jillian Dargatz ◽  
...  
Keyword(s):  
Integrin Αvβ3 ◽  
In Vivo Model ◽  
Vegf Receptor ◽  
Dependent Manner ◽  
Vascular Endothelial ◽  
Kinase Activation ◽  
Vegf Signaling ◽  
Endothelial Growth Factor

Abstract Vascular endothelial growth factor (VEGF) acting through VEGF receptor 2 (VEGFR2) on endothelial cells (ECs) is a key regulator of angiogenesis, a process essential for wound healing and tumor metastasis. Rap1a and Rap1b, 2 highly homologous small G proteins, are both required for angiogenesis in vivo and for normal EC responses to VEGF. Here we sought to determine the mechanism through which Rap1 promotes VEGF-mediated angiogenesis. Using lineage-restricted Rap1-knockout mice we show that Rap1-deficiency in endothelium leads to defective angiogenesis in vivo, in a dose-dependent manner. Using ECs obtained from Rap1-deficient mice we demonstrate that Rap1b promotes VEGF-VEGFR2 kinase activation and regulates integrin activation. Importantly, the Rap1b-dependent VEGF-VEGFR2 activation is in part mediated via integrin αvβ3. Furthermore, in an in vivo model of zebrafish angiogenesis, we demonstrate that Rap1b is essential for the sprouting of intersomitic vessels, a process known to be dependent on VEGF signaling. Using 2 distinct pharmacologic VEGFR2 inhibitors we show that Rap1b and VEGFR2 act additively to control angiogenesis in vivo. We conclude that Rap1b promotes VEGF-mediated angiogenesis by promoting VEGFR2 activation in ECs via integrin αvβ3. These results provide a novel insight into the role of Rap1 in VEGF signaling in ECs.

scholarly journals The Role of Vascular Endothelial Growth Factor in Systemic Sclerosis

2019 ◽  
Vol 15 (2) ◽  
pp. 99-109 ◽  
Author(s):  
Victoria A. Flower ◽  
Shaney L. Barratt ◽  
Stephen Ward ◽  
John D. Pauling
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Systemic Sclerosis ◽  
Growth Factor ◽  
Current Treatment ◽  
Vascular Endothelial ◽  
Vegf Signaling ◽  
Splice Isoform ◽  
Isoform Expression ◽  
Endothelial Growth Factor

The pathological hallmarks of Systemic Sclerosis (SSc) constitute an inter-related triad of autoimmunity, vasculopathy and tissue remodeling. Many signaling mediators have been implicated in SSc pathology; most focusing on individual components of this pathogenic triad and current treatment paradigms tend to approach management of such as distinct entities. The present review shall examine the role of Vascular Endothelial Growth Factor (VEGF) in SSc pathogenesis. We shall outline potential mechanisms whereby differential Vascular Endothelial Growth Factor-A (VEGF-A) isoform expression (through conventional and alternative VEGF-A splicing,) may influence the relevant burden of vasculopathy and fibrosis offering novel insight into clinical heterogeneity and disease progression in SSc. Emerging therapeutic approaches targeting VEGF signaling pathways might play an important role in the management of SSc, and differential VEGF-A splice isoform expression may provide a tool for personalized medicine approaches to disease management.

scholarly journals Pathogenesis of Preeclampsia and Therapeutic Approaches Targeting the Placenta

Biomolecules ◽  
2020 ◽  
Vol 10 (6) ◽  
pp. 953 ◽  
Author(s):  
Manoj Kumar Jena ◽  
Neeta Raj Sharma ◽  
Matthew Petitt ◽  
Devika Maulik ◽  
Nihar Ranjan Nayak
Keyword(s):  
Growth Factor ◽  
Clinical Symptoms ◽  
Growth Factor Receptor ◽  
Target Cells ◽  
Vascular Endothelial ◽  
Vegf Signaling ◽  
Endothelial Growth Factor ◽  
Maternal Disease ◽  
Placental Ischemia

Preeclampsia (PE) is a serious pregnancy complication, affecting about 5–7% of pregnancies worldwide and is characterized by hypertension and damage to multiple maternal organs, primarily the liver and kidneys. PE usually begins after 20 weeks’ gestation and, if left untreated, can lead to serious complications and lifelong disabilities—even death—in both the mother and the infant. As delivery is the only cure for the disease, treatment is primarily focused on the management of blood pressure and other clinical symptoms. The pathogenesis of PE is still not clear. Abnormal spiral artery remodeling, placental ischemia and a resulting increase in the circulating levels of vascular endothelial growth factor receptor-1 (VEGFR-1), also called soluble fms-like tyrosine kinase-1 (sFlt-1), are believed to be among the primary pathologies associated with PE. sFlt-1 is produced mainly in the placenta during pregnancy and acts as a decoy receptor, binding to free VEGF (VEGF-A) and placental growth factor (PlGF), resulting in the decreased bioavailability of each to target cells. Despite the pathogenic effects of increased sFlt-1 on the maternal vasculature, recent studies from our laboratory and others have strongly indicated that the increase in sFlt-1 in PE may fulfill critical protective functions in preeclamptic pregnancies. Thus, further studies on the roles of sFlt-1 in normal and preeclamptic pregnancies are warranted for the development of therapeutic strategies targeting VEGF signaling for the treatment of PE. Another impediment to the treatment of PE is the lack of suitable methods for delivery of cargo to placental cells, as PE is believed to be of placental origin and most available therapies for PE adversely impact both the mother and the fetus. The present review discusses the pathogenesis of PE, the complex role of sFlt-1 in maternal disease and fetal protection, and the recently developed placenta-targeted drug delivery system for the potential treatment of PE with candidate therapeutic agents.

scholarly journals Deficiency in the p110α subunit of PI3K results in diminished Tie2 expression and Tie2-/-–like vascular defects in mice

Blood ◽  
2005 ◽  
Vol 105 (10) ◽  
pp. 3935-3938 ◽  
Author(s):  
Etienne Lelievre ◽  
Pierre-Marie Bourbon ◽  
Li-Juan Duan ◽  
Robert L. Nussbaum ◽  
Guo-Hua Fong
Keyword(s):  
Tyrosine Kinases ◽  
Branching Morphogenesis ◽  
Vascular Endothelial ◽  
Mouse Development ◽  
Protein Levels ◽  
Upstream Regulator ◽  
Phosphoinositide 3 Kinase ◽  
Endothelial Growth Factor

AbstractPhosphoinositide 3-kinase (PI3K) is activated by transmembrane tyrosine kinases such as vascular endothelial growth factor (VEGF) receptors and Tie2 (tunica intima endothelial kinase 2), both of which are key regulators of vascular development. However, the in vivo role of PI3K during developmental vascularization remains to be defined. Here we demonstrate that mice deficient in the p110α catalytic subunit of PI3K display multiple vascular defects, including dilated vessels in the head, reduced branching morphogenesis in the endocardium, lack of hierarchical order of large and small branches in the yolk sac, and impaired development of anterior cardinal veins. These vascular defects are strikingly similar to those in mice defective in the Tie2 signaling pathway. Indeed, Tie2 protein levels were significantly lower in p110α-deficient mice. Furthermore, RNA interference of p110α in cultured endothelial cells significantly reduced Tie2 protein levels. These findings raise the possibility that PI3K may function as an upstream regulator of Tie2 expression during mouse development.

scholarly journals The role of vascular endothelial growth factor in the regulation of development and functioning of the brain: new target molecules for pharmacotherapy

2016 ◽  
Vol 62 (2) ◽  
pp. 124-133 ◽  
Author(s):  
V.V. Roslavtceva ◽  
A.B. Salmina ◽  
S.V. Prokopenko ◽  
E.A. Pozhilenkova ◽  
I.V. Kobanenko ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Neurological Diseases ◽  
Vascular Endothelial Growth Factors ◽  
Vascular Endothelial ◽  
Vegf Signaling ◽  
Target Molecules ◽  
Endothelial Growth Factor ◽  
Endothelial Growth Factors ◽  
The Brain

Vascular endothelial growth factors (VEGFs) have been shown to participate in atherosclerosis, arteriogenesis, cerebral edema, neuroprotection, neurogenesis, angiogenesis, postischemic brain and vessel repair. Most of these actions involve VEGF-A and the VEGFR-2 receptor. VEGF signaling pathways represent an important potential for treatment of neurological diseases affecting the brain

scholarly journals Manipulation of Quercetin and Melatonin in the Down-Regulation of HIF-1α, HSP-70 and VEGF Pathways in Rat’s Kidneys Induced by Hypoxic Stress

Dose-Response ◽  
2020 ◽  
Vol 18 (3) ◽  
pp. 155932582094979
Author(s):  
Aliah R. Alshanwani ◽  
Sameerah Shaheen ◽  
Laila M. Faddah ◽  
Ahlam M. Alhusaini ◽  
Hanaa M. Ali ◽  
...  
Keyword(s):  
Inflammatory Responses ◽  
Histopathological Examination ◽  
Hemoglobin Concentration ◽  
Vascular Endothelial ◽  
Hsp 70 ◽  
Reactive Protein ◽  
Defensive Role ◽  
Factor Α ◽  
Endothelial Growth Factor

Hypoxia may lead to inflammatory responses by numerous signaling pathways. This investigation intended to inspect the defensive role of Quercetin (Quer) and/ or Melatonin (Mel) against reno toxicity induced by Sodium nitrite (Sod ntr). Sod ntr injection significantly decreased blood hemoglobin concentration (Hb) with a concurrent increase in serum tumor necrosis factor- α, interleukin-6, C-reactive protein, creatinine, and urea levels. Over protein-expression of vascular endothelial growth factor and heat shock, protein-70 and mRNA of HIF-1α were also observed. Pretreatment of the Sod ntr- injected rats with the aforementioned antioxidants; either alone or together significantly improved such parameters. Histopathological examination reinforced the previous results. It was concluded that the combined administration of Quer and Mel may be useful as a potential therapy against renal injury induced by Sod ntr. HIF-1α and HSP-70 are implicated in the induction of hypoxia and its treatment.

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