Computational and Biochemical Discovery of RSK2 as a Novel Target for Epigallocatechin Gallate (EGCG)

Chen, Hanyong; Yao, Ke; Chang, Xiaoyu; Shim, Jung‐Hyun; Kim, Hong Gyum; Malakhova, Margarita; Kim, Dong Joon; Bode, Ann M.; Dong, Zigang

doi:10.1371/journal.pone.0130049

Cited by 12 publications

(7 citation statements)

References 43 publications

(64 reference statements)

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“…Chen et al predicted that a serine/threonine kinase, 90-kDa ribosomal S6 kinase (RSK2), would be a molecular target of EGCG [ 33 ]. CMDA, when combined with a pull-down assay, indicated that EGCG binds to RSK2 at catalytic domains in vitro and ex vivo.…”

Section: Cmda Of Catechin-protein Interactionmentioning

confidence: 99%

Computational Molecular Docking and X-ray Crystallographic Studies of Catechins in New Drug Design Strategies

et al. 2018

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Epidemiological and laboratory studies have shown that green tea and green tea catechins exert beneficial effects on a variety of diseases, including cancer, metabolic syndrome, infectious diseases, and neurodegenerative diseases. In most cases, (−)-epigallocatechin gallate (EGCG) has been shown to play a central role in these effects by green tea. Catechins from other plant sources have also shown health benefits. Many studies have revealed that the binding of EGCG and other catechins to proteins is involved in its action mechanism. Computational docking analysis (CMDA) and X-ray crystallographic analysis (XCA) have provided detailed information on catechin-protein interactions. Several of these studies have revealed that the galloyl moiety anchors it to the cleft of proteins through interactions with its hydroxyl groups, explaining the higher activity of galloylated catechins such as EGCG and epicatechin gallate than non-galloylated catechins. In this paper, we review the results of CMDA and XCA of EGCG and other plant catechins to understand catechin-protein interactions with the expectation of developing new drugs with health-promoting properties.

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Section: Cmda Of Catechin-protein Interactionmentioning

confidence: 99%

Computational Molecular Docking and X-ray Crystallographic Studies of Catechins in New Drug Design Strategies

et al. 2018

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“…After screening 68 kinases related to inflammation, we found that osajin inhibits RSK2 in an ATPcompetitive manner. Previous studies show that RSK2 is targeted by kaempferol and epigallocatechin gallate which have similar structure with osajin [Yao et al, 2014;Chen et al, 2015]. Based on Fig.…”

Section: Discussionmentioning

confidence: 91%

“…It is activated by cellular stresses such as sUV [Cho et al, 2012]. Previous studies show that RSK2 is targeted by kaempferol and epigallocatechin gallate which have similar structure with osajin [Yao et al, 2014;Chen et al, 2015]. Previous studies show that RSK2 is targeted by kaempferol and epigallocatechin gallate which have similar structure with osajin [Yao et al, 2014;Chen et al, 2015].…”

Section: Discussionmentioning

confidence: 99%

Osajin Inhibits Solar UV‐Induced Cyclooxygenase‐2 Expression Through Direct Inhibition of RSK2

Kim

Heo

Lee

2017

J of Cellular Biochemistry

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Solar ultraviolet light (sUV) has been shown to promote the development of skin disorders including inflammation, photoaging, and skin carcinogenesis. Osajin is the major bioactive isoflavone present in the fruit of Maclura pomifera, commonly referred to as the Osage orange. In this study, we observed that osajin inhibited sUV-induced cyclooxygenase (COX)-2 protein expression in both HaCaT and JB6 cells. COX-2 is a major mediator of skin inflammation. sUV activated the transcription factors nuclear factor-κB and activator protein-1 which, in turn, induces COX-2 expression. Osajin inhibited transactivation of these transcription factors. We identified RSK2 as an inhibitory target of osajin by screening against 68 kinases related to inflammation. Osajin binds with RSK2 directly in an ATP-competitive manner. Computer modeling simulated a plausible binding orientation between osajin and RSK2. Osajin inhibited sUV-induced phosphorylation of histone H3, a substrate of RSK2. However, sUV-induced phosphorylation of extracellular signal-regulated kinases, p38 kinase, c-Jun N-terminal kinase and Akt, which are signaling factors upstream of RSK2, was unchanged in the presence of osajin. The anti-inflammatory effects and molecular mechanism of osajin suggest that it may have utility as a functional food for skin health and cosmetic ingredient. J. Cell. Biochem. 118: 4080-4087, 2017. © 2017 Wiley Periodicals, Inc.

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“…EGCG has been demonstrated to have maximum relative efficiency of cellular DNA breakage whereas catechin was reported to possess minimum efficiency [47]. In another study, ribosomal protein S6 kinase (RSK)-2 has been established as a novel molecular target of EGCG using computational docking screening methods [48]. Other studies have suggested that the combination of EGCG and green tea extracts inhibit tumor growth in a xenograft mouse model of several human cancer cell lines.…”

Section: Catechinsmentioning

confidence: 99%

Role of Phytochemicals in Cancer Prevention

Ranjan

Ramachandran

Gupta

et al. 2019

IJMS

274

128

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The use of synthetic, natural, or biological agents to minimize the occurrence of cancer in healthy individuals is defined as cancer chemoprevention. Chemopreventive agents inhibit the development of cancer either by impeding DNA damage, which leads to malignancy or by reversing or blocking the division of premalignant cells with DNA damage. The benefit of this approach has been demonstrated in clinical trials of breast, prostate, and colon cancer. The continuous increase in cancer cases, failure of conventional chemotherapies to control cancer, and excessive toxicity of chemotherapies clearly demand an alternative approach. The first trial to show benefit of chemoprevention was undertaken in breast cancer patients with the use of tamoxifen, which demonstrated a significant decrease in invasive breast cancer. The success of using chemopreventive agents for protecting the high risk populations from cancer indicates that the strategy is rational and promising. Dietary components such as capsaicin, cucurbitacin B, isoflavones, catechins, lycopenes, benzyl isothiocyanate, phenethyl isothiocyanate, and piperlongumine have demonstrated inhibitory effects on cancer cells indicating that they may serve as chemopreventive agents. In this review, we have addressed the mechanism of chemopreventive and anticancer effects of several natural agents.

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Computational and Biochemical Discovery of RSK2 as a Novel Target for Epigallocatechin Gallate (EGCG)

Cited by 12 publications

References 43 publications

Computational Molecular Docking and X-ray Crystallographic Studies of Catechins in New Drug Design Strategies

Computational Molecular Docking and X-ray Crystallographic Studies of Catechins in New Drug Design Strategies

Osajin Inhibits Solar UV‐Induced Cyclooxygenase‐2 Expression Through Direct Inhibition of RSK2

Role of Phytochemicals in Cancer Prevention

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