α-Melanocyte-stimulating hormone inhibits angiogenesis through attenuation of VEGF/VEGFR2 signaling pathway

Weng, Wen-Tsan; Huang, Shih-Chung; Ma, Yi-Ling; Chan, Hoi‐Hung; Lin, Shih Pin; Wu, Jian-Ching; Wu, Chang‐Yi; Wen, Zhi‐Hong; Wang, E‐Ming; Wu, Chao‐Liang; Tai, Ming Hong

doi:10.1016/j.bbagen.2014.02.005

Cited by 17 publications

(22 citation statements)

References 39 publications

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“…The present study demonstrates the efficacy of MTII in suppressing the tumorigenicity of B16-F10 melanoma cells in vitro and in vivo. This finding is in agreement with previous studies using POMC gene therapy or α-MSH [25,[32][33][34]. Furthermore, animals receiving topical MTII therapy showed no obvious changes in activity, food uptake, and body weight (data not shown), implicating topical MTII therapy seemed to be well tolerated in mice bearing melanoma.…”

Section: Discussionsupporting

confidence: 92%

“…Consistently, our previous studies have demonstrated that the gene delivery of proopiomelanocortin (POMC), the precursor of alpha-melanocyte stimulating hormone (α-MSH), effectively suppresses the progression and metastasis of melanoma though the inhibition of COX-2/PGE2 signaling [24]. Among the POMC-derived peptides, α-MSH has been delineated to participate in the anti-neoplastic mechanism of POMC gene therapy via inflammation inhibition [24], neovascularization blockade [25,26], and sensitizing cancer cells to hypoxia-induced apoptosis [27].…”

Section: Introductionmentioning

confidence: 65%

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Topical MTII Therapy Suppresses Melanoma Through PTEN Upregulation and Cyclooxygenase II Inhibition

Tsai

Hsiao

et al. 2020

IJMS

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Melanotan II (MTII), a synthetic analogue of the alpha-melanocyte stimulating hormone (α-MSH), has been applied for skin tanning in humans. However, the carcinogenic consequence of topical MTII has been equivocal. This study aims to delineate the anti-neoplastic efficacy and mechanism of MTII using the B16-F10 melanoma model in vitro and in vivo. It was found that, despite a lack of influence on proliferation, MTII potently inhibited the migration, invasion, and colony-forming capability of melanoma cells. Moreover, topical MTII application significantly attenuated the tumor progression in mice bearing established melanoma. Histological analysis revealed that MTII therapy induced apoptosis while inhibiting the proliferation and neovaluarization in melanoma tissues. By immunoblot and immunohistochemical analysis, it was found that MTII dose-dependently increased the phosphatase and tensin homolog (PTEN) protein level while reducing PTEN phosphorylation, which resulted in the inhibition of AKT/nuclear factor kappa B (NFκB) signaling. Consistently, MTII treatment inhibited cyclooxygenase II (COX-2) expression and prostaglandin E2 (PGE2) production in melanoma cells. Finally, studies of antibody neutralization suggest that the melanocortin 1 receptor (MC1R) plays a critical role in MTII-induced PTEN upregulation and melanoma suppression. Together, these results indicate that MTII elicits PTEN upregulation via MC1R, thereby suppressing melanoma progression through downregulating COX-2/PGE2 signaling. Hence, topical MTII therapy may facilitate a novel therapeutic strategy against melanoma.

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Section: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 65%

Topical MTII Therapy Suppresses Melanoma Through PTEN Upregulation and Cyclooxygenase II Inhibition

Tsai

Hsiao

et al. 2020

IJMS

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“…Zebrafish ( Danio rerio ) transgenic lines: Tg(fli-1:EGFP) y1 , in which the enhanced green fluorescent proteins (EGFP) is expressed in all endothelial cells of the vasculature [ 33 , 34 ] and Tg(kdrl:mCherry ci5 -fli1a:negfp y7 ), in which endothelial cells are labeled with green nuclei by nuclear enhanced green fluorescent protein (nEGFP) expression and the vessels are labeled with red by cytoplasmic mCherry expression, were obtained from the Taiwan Zebrafish Core Facility (Academia Sinica, Taipei, Taiwan). Zebrafish were raised and maintained at the 28.5 °C incubator accordance with The Zebrafish Book [ 35 ] with approval from the National Sun Yat-Sen University Animal Care Committee.…”

Section: Methodsmentioning

confidence: 99%

Coral-Derived Compound WA-25 Inhibits Angiogenesis by Attenuating the VEGF/VEGFR2 Signaling Pathway

et al. 2015

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Background: WA-25 (dihydroaustrasulfone alcohol, a synthetic derivative of marine compound WE-2) suppresses atherosclerosis in rats by reducing neointima formation. Because angiogenesis plays a critical role in the pathogenesis of atherosclerosis, the present study investigated the angiogenic function and mechanism of WA-25. Methods: The angiogenic effect of WA-25 was evaluated using a rat aortic ring assay and transgenic zebrafish models were established using transgenic Tg(fli-1:EGFP)y1 and Tg(kdrl:mCherryci5-fli1a:negfpy7) zebrafish embryos. In addition, the effect of WA-25 on distinct angiogenic processes, including matrix metalloproteinase (MMP) expression, endothelial cell proliferation and migration, as well as tube formation, was studied using human umbilical vein endothelial cells (HUVECs). The effect of WA-25 on the endothelial vascular endothelial growth factor (VEGF) signaling pathway was elucidated using qRT-PCR, immunoblot analysis, immunofluorescence and flow cytometric analyses. Results: The application of WA-25 perturbed the development of intersegmental vessels in transgenic zebrafish. Moreover, WA-25 potently suppressed microvessel sprouting in organotypic rat aortic rings. Among cultured endothelial cells, WA-25 significantly and dose-dependently inhibited MMP-2/MMP-9 expression, proliferation, migration and tube formation in HUVECs. Mechanistic studies revealed that WA-25 significantly reduced the VEGF release by reducing VEGF expression at the mRNA and protein levels. In addition, WA-25 reduced surface VEGF receptor 2 (VEGFR2/Flk-1) expression by repressing the VEGFR2 mRNA level. Finally, an exogenous VEGF supply partially rescued the WA-25-induced angiogenesis blockage in vitro and in vivo. Conclusions: WA-25 is a potent angiogenesis inhibitor that acts through the down-regulation of VEGF and VEGFR2 in endothelial cells. General Significance: WA-25 may constitute a novel anti-angiogenic drug that acts by targeting endothelial VEGF/VEGFR2 signaling.

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“…Furthermore, it was shown that the downstream effector of VEGF, Akt, was inactivated. Of note, excessive VEGF supply did not substantially reverse the α-MSH-induced inhibition of angiogenesis in vitro [19]. This suggests that while inhibition of the VEGF/VEGFR-2/Akt pathway may contribute, there are other mechanisms involved in α-MSH inhibition of angiogenesis left to be discovered.…”

Section: α-Melanocyte-stimulating Hormonementioning

confidence: 99%

“…It is believed that angiogenesis sustains inflammation by delivering oxygen and nutrients to support the increased metabolic needs of cells at sites of inflammation [18]. It has recently been shown that α-MSH inhibits angiogenesis by attenuating vascular endothelial growth factor (VEGF) signaling in endothelial cells [19]. This study showed that the binding of α-MSH to melanocortin receptors 1 and 2 caused inhibition of metalloproteinase secretion, inhibition of endothelial cell migration, and inhibition of tube formation of endothelial cells.…”

Section: α-Melanocyte-stimulating Hormonementioning

confidence: 99%

Immunoregulatory Effects of Neuropeptides on Endothelial Cells: Relevance to Dermatological Disorders

Mehta

Granstein²

2019

Dermatology

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Many skin diseases, including psoriasis and atopic dermatitis, have a neurogenic component. In this regard, bidirectional interactions between components of the nervous system and multiple target cells in the skin and elsewhere have been receiving increasing attention. Neuropeptides released by sensory nerves that innervate the skin can directly modulate functions of keratinocytes, Langerhans cells, dermal dendritic cells, mast cells, dermal microvascular endothelial cells and infiltrating immune cells. As a result, neuropeptides and neuropeptide receptors participate in a complex, interdependent network of mediators that modulate the skin immune system, skin inflammation, and wound healing. In this review, we will focus on recent studies demonstrating the roles of α-melanocyte-stimulating hormone, calcitonin gene-related peptide, substance P, somatostatin, vasoactive intestinal peptide, pituitary adenylate cyclase-activating peptide, and nerve growth factor in modulating inflammation and immunity in the skin through their effects on dermal microvascular endothelial cells.

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α-Melanocyte-stimulating hormone inhibits angiogenesis through attenuation of VEGF/VEGFR2 signaling pathway

Cited by 17 publications

References 39 publications

Topical MTII Therapy Suppresses Melanoma Through PTEN Upregulation and Cyclooxygenase II Inhibition

Topical MTII Therapy Suppresses Melanoma Through PTEN Upregulation and Cyclooxygenase II Inhibition

Coral-Derived Compound WA-25 Inhibits Angiogenesis by Attenuating the VEGF/VEGFR2 Signaling Pathway

Immunoregulatory Effects of Neuropeptides on Endothelial Cells: Relevance to Dermatological Disorders

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