Ethyl pyruvate, an anti-inflammatory agent, inhibits tumor angiogenesis through inhibition of the NF-κB signaling pathway

Park, Shi-Young; Yi, Eui-Yeun; Jung, M.J.; Lee, You Mie; Kim, Yung-Jin

doi:10.1016/j.canlet.2010.12.024

Cited by 25 publications

(20 citation statements)

References 19 publications

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“…Due to the critical role of inflammation in both tumor initiation and progression, in recent years, several groups have studied the possible therapeutic effects of EP on cancer [32, 34, 35, 40–42]. It was found that EP is able to reduce tumor development and increase the overall survival of animals in different tumor models, such as liver, gastric and gallbladder.…”

Section: Discussionmentioning

confidence: 99%

HMGB1 targeting by ethyl pyruvate suppresses malignant phenotype of human mesothelioma

et al. 2017

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Human malignant mesothelioma (MM) is an aggressive cancer linked to asbestos and erionite exposure. We previously reported that High-Mobility Group Box-1 protein (HMGB1), a prototypic damage-associated molecular pattern, drives MM development and sustains MM progression. Moreover, we demonstrated that targeting HMGB1 inhibited MM cell growth and motility in vitro, reduced tumor growth in vivo, and prolonged survival of MM-bearing mice. Ethyl pyruvate (EP), the ethyl ester of pyruvic acid, has been shown to be an effective HMGB1 inhibitor in inflammation-related diseases and several cancers. Here, we studied the effect of EP on the malignant phenotype of MM cells in tissue culture and on tumor growth in vivo using an orthotopic MM xenograft model. We found that EP impairs HMGB1 secretion by MM cells leading to reduced RAGE expression and NF-κB activation. As a consequence, EP impaired cell motility, cell proliferation, and anchorage-independent growth of MM cells. Moreover, EP reduced HMGB1 serum levels in mice and inhibited the growth of MM xenografts.Our results indicate that EP effectively hampers the malignant phenotype of MM, offering a novel potential therapeutic approach to patients afflicted with this dismal disease.

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Section: Discussionmentioning

confidence: 99%

HMGB1 targeting by ethyl pyruvate suppresses malignant phenotype of human mesothelioma

et al. 2017

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“…Ethyl pyruvate, a ROS scavenger, has been found to ameliorate in different conditions such as sepsis, acute pancreatitis, burn, radiation injury and hemorrhagic shock[98,99]. Turkmen et al[100] reported that ethyl pyruvate has a positive effect on torsion-detorsion associated I/R injury in an experimental rat model.…”

Section: Searchmentioning

confidence: 99%

Antioxidants in experimental ischemia-reperfusion injury of the testis: Where are we heading towards?

Vaos

Zavras

2017

WJM

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Testicular torsion (TT) is a medical emergency that primary affects newborns and young adolescents. It causes testicular injury due to the torsion of the spermatic cord and its components, initially in the venous blood flow and finally in the arterial blood flow. Prompt diagnosis and early surgical management are necessary in managing this urgent situation. The process of the pathophysiological events in ischemia-reperfusion is multifactorial and deals with the perception of the oxidative stress responsible for the consequences of ischemia/reperfusion (I/R) stress following TT. Duration and severity of torsion also play a significant role in the oxidative stress. A detrimental result of the defense system of the testes takes place resulting finally in testicular atrophy and impaired function. Antioxidant factors have been experimentally studied in an effort to front this state. They have been classified as endogenous or exogenous antioxidants. Endogenous antioxidants comprise a structure of enzymic enzymatic and non-enzymic enzymatic particles presented within cytoplasm and numerous other subunits in the cells. Exogenous antioxidants include a variety of natural and pharmaceutical agents that may prevent or ameliorate the harmful effects of I/R injury. In this study we review those factors and their ability to enhance the oxidative status of the testis. A feature insight into where we are heading is attempted.

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“…EP is also a potent HMGB1 inhibitor [15]. Moreover, EP inhibits tumor angiogenesis and intracerebral hemorrhage-induced angiogenesis [16, 17]. However, the pathogenic role of HMGB1 and the effect of its inhibitor, EP, in pathological retinal neovascularization have remained uncertain.…”

Section: Introductionmentioning

confidence: 99%

Ethyl Pyruvate Inhibits Retinal Pathogenic Neovascularization by Downregulating HMGB1 Expression

Lee

Kim

et al. 2013

Journal of Diabetes Research

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Retinal pathogenic angiogenesis in the eyes is a causative factor in retinopathy of prematurity, diabetic retinopathy, and age-related macular degeneration. This study was designed to examine the pathogenic role of the high-mobility group box-1 (HMGB1) protein and the inhibitory effect of ethyl pyruvate (EP), a well-known antioxidant substance, in retinal pathogenic angiogenesis in mice with oxygen-induced retinopathy (OIR), one of the animal models of proliferative ischemic retinopathy. The OIR mouse model was used for our in vivo studies. The mice were exposed to 75% oxygen from postnatal day 7 (P7) to P11, after which the mice were brought to room air and intraperitoneally injected with EP (50 mg/kg, or 100 mg/kg) for five days. At P17, the mice were perfused with fluorescein isothiocyanate-dextran, and flat-mounted retinas were used to measure nonperfused and neovascular tufts. In OIR mice, an intraperitoneal injection of EP reduced the nonperfused retinal area in the treatment group and significantly reduced the retinal neovascular tufts. In addition, EP inhibited the overexpression of HMGB1 in the retinas of OIR mice. These data suggest that EP could serve as an innovative pharmaceutical agent to prevent retinal neovascularization through inhibiting HMGB1 expression.

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Ethyl pyruvate, an anti-inflammatory agent, inhibits tumor angiogenesis through inhibition of the NF-κB signaling pathway

Cited by 25 publications

References 19 publications

HMGB1 targeting by ethyl pyruvate suppresses malignant phenotype of human mesothelioma

HMGB1 targeting by ethyl pyruvate suppresses malignant phenotype of human mesothelioma

Antioxidants in experimental ischemia-reperfusion injury of the testis: Where are we heading towards?

Ethyl Pyruvate Inhibits Retinal Pathogenic Neovascularization by Downregulating HMGB1 Expression

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