The Vascular Endothelial Growth Factor (VEGF) Signaling Pathway: A Therapeutic Target in Patients with Hematologic Malignancies

Giles, Francis J.

doi:10.1634/theoncologist.6-2004-32

Cited by 8 publications

(7 citation statements)

References 33 publications

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“…Vascular endothelial growth factor (VEGF) is a key angiogenic factor that regulates several endothelial cell functions, particularly mitogenesis. It was shown that the levels of VEGF in association with poor prognosis is raised in hematologic malignancies (Giles, 2001).…”

Section: Inhibition Of Vegf/hsp27 Signaling Pathwaymentioning

confidence: 99%

Leukemia therapy by flavonoids: Future and involved mechanisms

Saraei

Marofi

Naimi

et al. 2018

Journal Cellular Physiology

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Flavonoids are a varied family of phytonutrients (plant chemicals) usually are detected in fruits and vegetables. In this big family, there exist more than 10,000 members that is separated into six chief subtypes: isoflavonols, flavonoenes, flavones, flavonols, anthocyanins, and chalcones. The natural compounds, such as fruits, have visible positive effects in regulating of survival involved signaling pathways that performance as the regulator of cell survival, growth, and proliferation. Researchers have established that commonly consumption up flavonoids decreases incidence and development risk of certain cancers, especially leukemia. Flavonoids have been able to induce apoptosis and stimulate cell cycle arrest in cancer cells via different pathways. Similarly, they have antiangiogenesis and antimetastasis capability, which were shown in wide ranges of cancer cells, particularly, leukemia. It seems that flavonoid because of their widespread approval, evident safety and low rate of side effects, have hopeful anticarcinogenic potential for leukemia therapy. Based on the last decade reports, the most important acting mechanisms of these natural compounds in leukemia cells are stimulating of apoptosis pathways by upregulation of caspase 3, 8, 9 and poly ADP‐ribose polymerase (PARP) and proapoptotic proteins, particularly Bax activation. As well, they can induce cell cycle arrest in target cells not only via increasing of activated levels of p21 and p53 but also by inhibition of cyclins and cyclin‐dependent kinases. Furthermore, attenuation of neclear factor‐κB and signal transducer and activator of transcription 3 activation, suppression of signaling pathway and downregulation of intracellular antiapoptotic proteins are other significant antileukemic function mechanism of flavonoids. Overall, it appears that flavonoids are promising and effective compounds in the field of leukemia therapy. In this review, we tried to accumulate and revise most promising flavonoids and finally declared their major working mechanisms in leukemia cells.

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Section: Inhibition Of Vegf/hsp27 Signaling Pathwaymentioning

confidence: 99%

Leukemia therapy by flavonoids: Future and involved mechanisms

Saraei

Marofi

Naimi

et al. 2018

Journal Cellular Physiology

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“…Angiogenesis, the process resulting in the formation of new blood vessels from pre-existing ones, plays an important role in the development and destabilisation of atherosclerotic plaques [6][7][8]. Vascular endothelial growth factor (VEGF) has been shown to be the most important pro-angiogenic growth factor in humans [9][10][11] exerting its angiogenic effects by stimulating VEGF receptor 2 (VEGFR-2), which is critical for promoting proliferation and differentiation of endothelial cells [11,12]. Indeed, it has been demonstrated directly that VEGF drives the growth of existing plaques in high fat diet-fed New Zealand White rabbits and hypercholesteraemic ApoE −/− mice [13,14].…”

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confidence: 99%

Molecular structure‐function relationship of dietary polyphenols for inhibiting VEGF‐induced VEGFR‐2 activity

Cerezo

Winterbone

Moyle

et al. 2015

Molecular Nutrition Food Res

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ScopeWe recently reported potent inhibition of VEGF signalling by two flavanols at sub‐micromolar concentrations, mediated by direct binding of the flavanols to VEGF. The aim of this study was to quantify the inhibitory potency and binding affinity of a wide range of dietary polyphenols and determine the structural requirements for VEGF inhibition.Methods and resultsThe concentration of polyphenol required to cause 50% inhibition (IC50) of VEGF‐dependent VEGFR‐2 activation in HUVECS was determined after pretreating VEGF with polyphenols at various concentations. Binding affinities and binding sites on VEGF were predicted using in‐silico modelling. Ellagic acid and 15 flavonoids had IC50 values ≤10 μM while 28 other polyhenols were weak/non‐inhibitors. Structural features associated with potent inhibition included 3‐galloylation, C‐ring C2=C3, total OH, B‐ring catechol, C‐ring 3‐OH of flavonoids. Potency was not associated with polyphenol hydrophobicity. There was a strong correlation between potency of inhibition and binding affinities, and all polyphenols were predicted to bind to a region on VEGF involved in VEGFR‐2 binding.ConclusionSpecific polyphenols bind directly to a discrete region of VEGF and inhibit VEGF signalling, and this potentially explains the associations between consumption of these polyphenols and CVD risk.

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“…VEGF expression in many solid tumors has been shown to be a marker of poor prognosis including breast, renal, oropharyngeal, colon, gastric, and lung cancers (10)(11)(12)(13)(14)(15). Several recent reports have implicated VEGF as a powerful prognostic indicator in many hematologic malignancies as well as acute (16) and chronic myeloid leukemia (17), chronic lymphocytic leukemia (18), non-Hodgkin's lymphoma (19), Hodgkin's disease (20), and myelodysplastic syndromes (21).…”

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confidence: 99%

Bone marrow expression of vascular endothelial growth factor in myelofibrosis with myeloid metaplasia

Arora

Hoyer

et al. 2004

European J of Haematology

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The biologic relevance and prognostic impact of angiogenesis is being increasingly recognized in many solid tumors and hematologic malignancies including myelofibrosis with myeloid metaplasia (MMM). Many cytokines including vascular endothelial growth factor (VEGF) have been implicated for neoangiogenesis in MMM. However, the exact humoral basis remains to be elucidated. We examined the expression of VEGF by immunohistochemistry in a prospective cohort of 66 MMM patients, including six with cellular phase disease, and five normal controls. Contrary to most other hematologic malignancies, the distribution and intensity of staining for VEGF in bone marrow was similar between the MMM patients and controls. Interestingly, all six cellular phase patients displayed significantly increased VEGF expression. Thus, upregulation of angiogenic cytokines other than VEGF such as TGF-beta or loss of activity of an anti-angiogenic cytokine might be the dominant pathway of endothelial activation in MMM. However, VEGF might contribute to the process in the early stages of the disease.

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The Vascular Endothelial Growth Factor (VEGF) Signaling Pathway: A Therapeutic Target in Patients with Hematologic Malignancies

Cited by 8 publications

References 33 publications

Leukemia therapy by flavonoids: Future and involved mechanisms

Leukemia therapy by flavonoids: Future and involved mechanisms

Molecular structure‐function relationship of dietary polyphenols for inhibiting VEGF‐induced VEGFR‐2 activity

Bone marrow expression of vascular endothelial growth factor in myelofibrosis with myeloid metaplasia

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