Resveratrol inhibits <scp>VEGF</scp>‐induced angiogenesis in human endothelial cells associated with suppression of aerobic glycolysis via modulation of <scp>PKM</scp>2 nuclear translocation

Wu, Hongyan; He, Lin; Shi, Juanjuan; Hou, Xianbang; Zhang, Hong-Jiang; Zhang, Xiaoping; An, Qing; Fan, Fangtian

doi:10.1111/1440-1681.13017

Cited by 31 publications

(17 citation statements)

References 47 publications

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“…Resveratrol is one of the most promising antitumor drugs to inhibit cancer initiation, progression, and metastasis 14,17. Certainly, there are many studies that indicated that resveratrol can induce apoptosis in melanoma cells by inducing the expression of proapoptotic proteins 10.…”

Section: Discussionmentioning

confidence: 99%

“…First, Wu et al identified that resveratrol induced cancer cell apoptosis targeting M2-type pyruvate kinase (PKM2)-mediated ER stress and mitochondrial fission 14. Second, Yang et al and Wu et al evaluated that ERK1/2-dependent nuclear translocation of PKM2 promoted glucose metabolism in various cancer cells 16,17. Finally, Liang et al reported that mitochondrial PKM2 interacted with and phosphorylated Bcl-2, which then prevented the degradation of Bcl-2 and enhanced apoptosis resistance of tumor cells 18…”

Section: Introductionmentioning

confidence: 99%

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Resveratrol induces apoptosis in human melanoma cell through negatively regulating Erk/PKM2/Bcl-2 axis

Zhao¹,

Han²,

Yi³

et al. 2018

OTT

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BackgroundResveratrol is known as a natural phytoalexin found in grapes and wine, which has significant antitumor activity under in vitro and in vivo conditions. In recent years, great progress has been made in understanding the underlying mechanisms of resveratrol in inducing cellular apoptosis of melanoma cells. Our previous study has shown that the apoptosis regulation of resveratrol in melanoma cells was independent of activation of classical apoptosis-related protein p53.Materials and methodsMTT assay and 5-bromo-2′-deoxyuridine staining assay were used to analyze cell viability and proliferation. Immunofluorescence analysis of γ-H2AX was employed to clarify DNA damages. Annexin V–propidine iodide/fluorescein isothiocyanate assay was performed to evaluate the cell apoptosis. The mechanisms underlying the activation of M2-type pyruvate kinase (PKM2) by Erk1/2 to stabilize and maintain Bcl-2 signaling was investigated by subcellular fractionation analyses, immunofluorescence analysis, co-immunoprecipitation assay, ubiquitination assay, and glutathione S-transferase pull-down assay.ResultsIn the present study, we found that resveratrol dramatically inhibited melanoma cell proliferation and induced cell apoptosis through upregulation of p53 in a concentration-dependent manner. Conversely, p53 downregulation by short hairpin RNA couldn’t rescue resveratrol-induced cell proliferation inhibition or apoptosis enlargement. Additionally, we found that resveratrol downregulated antiapoptotic protein Bcl-2 and activated Bax in the protein levels by promoting Bcl-2 degradation and cytochrome c release. Moreover, we discovered that PKM2, had a key role in cell apoptosis triggered by resveratrol through interacting with Bcl-2. Based on these results, we overexpressed PKM2 in melanoma cells and found that this prevented resveratrol-induced apoptosis by stabilizing the protein level of Bcl-2.ConclusionTaken together, our results provided a novel mechanism accounting for the apoptosis induction of resveratrol in melanoma cells and suggested that downregulating Erk/PKM2/Bcl-2 axis appears to be a new approach for the prevention or treatment of melanoma.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Resveratrol induces apoptosis in human melanoma cell through negatively regulating Erk/PKM2/Bcl-2 axis

Zhao¹,

Han²,

Yi³

et al. 2018

OTT

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“…Resveratrol (RES) consists 3,5,40-trihydroxytrans-stilbene, and it is one of the best-studied phytophenols with pleiotropic properties. 63 , 64 Resveratrol inhibits VEGF-induced angiogenesis in endothelial cells 65 and inhibits TNF-α-induced keratinocyte proliferation and matrix metalloproteinase (MMP-9) expression by inhibiting nuclear factor (NF)-kappa B and activator protein-1 (AP-1). 65 RES also suppresses type I collagen deposition and keloid fibroblast proliferation.…”

Section: Discussionmentioning

confidence: 99%

<p>Polyphenol-Conjugated Bimetallic Au@AgNPs for Improved Wound Healing</p>

Orłowski

Żmigrodzka

Tomaszewska

et al. 2020

IJN

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Background Polyphenols possess antioxidant, anti-inflammatory and antimicrobial properties and have been used in the treatment of skin wounds and burns. We previously showed that tannic acid-modified AgNPs sized >26 nm promote wound healing, while tannic acid-modified AgNPs sized 13 nm can elicit strong local inflammatory response. In this study, we tested bimetallic Au@AgNPs sized 30 nm modified with selected flavonoid and non-flavonoid compounds for wound healing applications. Methods Bimetallic Au@AgNPs were obtained by growing an Ag layer on AuNPs and further modified with selected polyphenols. After toxicity tests and in vitro scratch assay in HaCaT cells, modified lymph node assay as well as the mouse splint wound model were further used to access the wound healing potential of selected non-toxic modifications. Results Tannic acid, gallic acid, polydatin, resveratrol, catechin, epicatechin, epigallocatechin, epicatechin gallate, epigallocatechin gallate and procyanidin B2 used to modify Au@AgNPs exhibited good toxicological profiles in HaCaT cells. Au@AgNPs modified with 15 μM tannic acid, 200 μM resveratrol, 200 μM epicatechin gallate, 1000 μM gallic acid and 200 μM procyanidin B2 induced wound healing in vivo and did not lead to the local irritation or inflammation. Tannic acid-modified Au@AgNPs induced epithelial-to-mesenchymal transition (EMT) – like re-epithelialization, while other polyphenol modifications of Au@AgNPs acted through proliferation and wound closure. Conclusion Bimetallic Au@AgNPs can be used as a basis for modification with selected polyphenols for topical uses. In addition, we have demonstrated that particular polyphenols used to modify bimetallic nanoparticles may show different effects upon different stages of wound healing.

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“…Treatment with VEGF on human endothelial cells (HUVEC cells) increased expression of proteins involved in glycolysis such as glucose transporter 1 (GLUT1), hexokinase 2 (HK2), phosphofructokinase 1 (PFK1), pyruvate kinase M2 isoform (PKM2), inducing tube formation and migration. However, these effects were reversed by resveratrol through downregulation of the glycolytic genes, suppression of ERK1/2 and nuclear translocation of PKM2 [87]. A recent study proposes that resveratrol inhibits VEGF signaling through direct interaction with VEGF.…”

Section: Modulation Of Angiogenesis By Resveratrolmentioning

confidence: 99%

Resveratrol as a Tumor-Suppressive Nutraceutical Modulating Tumor Microenvironment and Malignant Behaviors of Cancer

Han

Cho

et al. 2019

IJMS

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Tumor-suppressive effects of resveratrol have been shown in various types of cancer. However, regulation of tumor microenvironment by resveratrol is still unclear. Recent findings suggest resveratrol can potentiate its tumor-suppressive effect through modulation of the signaling pathways of cellular components (fibroblasts, macrophages and T cells). Also, studies have shown that resveratrol can suppress malignant phenotypes of cancer cells acquired in response to stresses of the tumor microenvironment, such as hypoxia, oxidative stress and inflammation. We discuss the effects of resveratrol on cancer cells in stress environment of tumors as well as interactions between cancer cells and non-cancer cells in this review.

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Resveratrol inhibits VEGF‐induced angiogenesis in human endothelial cells associated with suppression of aerobic glycolysis via modulation of PKM2 nuclear translocation

Cited by 31 publications

References 47 publications

Resveratrol induces apoptosis in human melanoma cell through negatively regulating Erk/PKM2/Bcl-2 axis

Resveratrol induces apoptosis in human melanoma cell through negatively regulating Erk/PKM2/Bcl-2 axis

<p>Polyphenol-Conjugated Bimetallic Au@AgNPs for Improved Wound Healing</p>

Resveratrol as a Tumor-Suppressive Nutraceutical Modulating Tumor Microenvironment and Malignant Behaviors of Cancer

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