Epigallocatechin-gallate Suppresses Tumorigenesis by Directly Targeting Pin1

Urusova, Darya V.; Shim, Jung‐Hyun; Kim, Dong Joon; Jung, Sung Keun; Zykova, Tatyana A.; Carper, Andria; Bode, Ann M.; Dong, Zigang

doi:10.1158/1940-6207.capr-11-0301

Cited by 105 publications

(106 citation statements)

References 43 publications

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“…H1299 and CL13 lung cancer cells highly express G3BP1, and EGCG effectively suppresses anchorage-independent growth of these cells but was less effective in cells with a low expression of G3BP1 (131). Finally, we (113,119,139) found that EGCG binds with the human peptidyl prolyl cis/trans isomerase [Pin1 (139)], which plays a critical role in oncogenic signaling (40,128). In this case, we were able to combine crystallography, computational biology and cell-and animal-based studies to identify Pin1 as a novel binding protein of EGCG.…”

Section: Other Protein Targets Of Flavonoidsmentioning

confidence: 84%

Signal Transduction and Molecular Targets of Selected Flavonoids

Bode

Dong

2013

Antioxidants & Redox Signaling

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Significance: Diet exerts a major influence on the risk for developing cancer and heart disease. Food factors such as flavonoids are alleged to protect cells from premature aging and disease by shielding DNA, proteins, and lipids from oxidative damage. Recent Advances: Our work has focused on clarifying the effects of dietary components on cancer cell proliferation and tumor growth, discovering mechanisms to explain the effects, and identifying the specific molecular targets of these compounds. Our strategy for identifying specific molecular targets of phytochemicals involves the use of supercomputer technology combined with protein crystallography, molecular biology, and experimental laboratory verification. Critical Issues: One of the greatest challenges for scientists is to reduce the accumulation of distortion and half truths reported in the popular media regarding the health benefits of certain foods or food supplements. The use of these is not new, but interest has increased dramatically because of perceived health benefits that are presumably acquired without unpleasant side effects. Flavonoids are touted to exert many beneficial effects in vitro. However, whether they can produce these effects in vivo is disputed. Future Directions: The World Health Organization indicates that one third of all cancer deaths are preventable and that diet is closely linked to prevention. Based on this idea and epidemiological findings, attention has centered on dietary phytochemicals as an effective intervention in cancer development. However, an unequivocal link between diet and cancer has not been established. Thus, identifying cancer preventive dietary agents with specific molecular targets is essential to move forward toward successful cancer prevention.

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Section: Other Protein Targets Of Flavonoidsmentioning

confidence: 84%

Signal Transduction and Molecular Targets of Selected Flavonoids

Bode

Dong

2013

Antioxidants & Redox Signaling

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“…Clearly, it will be important to identify which active components and molecular targets/mechanisms may be responsible for the efficacy of strawberries. Such work has recently been reported in regard to the epigallocatechin gallate component of green tea (41).…”

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confidence: 76%

Strawberry Fields Forever?

Suh¹,

Pezzuto

2012

Cancer Prevention Research

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On the basis of copious preclinical data supporting the preventive efficacy of small fruits such as berries and grapes, Chen and colleagues conducted a randomized (noncomparative) phase II trial evaluating two doses of strawberry powder (60 g/d or 30 g/d for six months) to prevent esophageal cancer in China (reported in this issue of the journal, beginning on page 41); 60 g/d reduced the histologic grade of dysplastic lesions and reduced localized biomarkers, whereas 30 g/d was not effective. Fundamental questions remain such as the best formulation of strawberry powder, the active components associated with powder, and the actual mechanism of action, and standardized preparations will be required to permit the widespread use of strawberry powder with a predicable outcome. Clearly, however, this work is a good example of proof-ofprinciple and highlights the important role of diet, nutrition, and natural products in cancer prevention. Cancer Prev Res; 5(1); 30-33. Ó2012 AACR.

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“…This method has been described previously (23,24). Briefly, PI3K active protein (2 µg) was reacted with Sepharose 4B beads or jugloneSepharose 4B beads in reaction buffer [50 mM Tris, pH 7.5, 5 mM ethylenediaminetetraacetic acid (EDTA), 150 mM NaCl, 1 mM dithiothreitol (DTT), 0.01% Nonidet P-40, 2 µg/ml bovine serum albumin, 0.02 mM phenylmethylsulfonyl fluoride (PMSF), and 1X proteinase inhibitor cocktail].…”

Section: Methodsmentioning

confidence: 99%

Phosphoinositol 3-kinase, a novel target molecule for the inhibitory effects of juglone on TPA-induced cell transformation

et al. 2012

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Abstract. Juglone (5-hydroxy-1,4-naphthalenedione) from black walnut trees induces apoptosis and inhibits proliferation of various malignant cells. Here, we investigated whether juglone affects 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced cell transformation through the phosphoinositol 3-kinase (PI3K) pathway. The results showed that TPA-and endothelial growth factor (EGF)-induced anchorage-independent colony formation were suppressed in a dose-dependent manner by treatment of JB6 CI41 mouse skin epidermal cells with juglone (2.5 and 5 µM). We demonstrated that juglone suppressed PI3K activity via direct binding to PI3K by sepharose 4B pulldown assay and western blot analysis. Juglone significantly suppressed TPA-induced protein kinase B (AKT) and c-Jun phosphorylation and c-fos activation, but not mitogen-activated protein-kinase kinase (MEK), extracellular signaling-regulated kinase (ERK) or 90 kDa ribosomal protein S6 kinase (RSK) phosphorylation. Juglone significantly blocked activator protein-1 (AP-1) and cyclooxygenase-2 (COX-2) activation more than the PI3K inhibitors LY294002 and wortmannin. Overall, these results showed the anticancer efficacy of juglone targeting PI3K to prevent TPA-induced tumorigenesis.

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Epigallocatechin-gallate Suppresses Tumorigenesis by Directly Targeting Pin1

Cited by 105 publications

References 43 publications

Signal Transduction and Molecular Targets of Selected Flavonoids

Signal Transduction and Molecular Targets of Selected Flavonoids

Strawberry Fields Forever?

Phosphoinositol 3-kinase, a novel target molecule for the inhibitory effects of juglone on TPA-induced cell transformation

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