Epigallocatechin-gallate suppresses tumorigenesis by directly targeting Pin1

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

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

Epigallocatechin-gallate suppresses tumorigenesis by directly targeting Pin1

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

School of Food Science & Biotechnology

Research output: Contribution to journal › Article › peer-review

111 Scopus citations

Abstract

The most active anticancer component in green tea is epigallocatechin-3- gallate (EGCG). The human peptidyl prolyl cis/trans isomerase (Pin1) plays a critical role in oncogenic signaling. Herein, we report the X-ray crystal structure of the Pin1/EGCGcomplex resolved at 1.9Å resolution.Notably, the structure revealed the presence of EGCG in both the WWand PPIase domains of Pin1. The direct binding of EGCG with Pin1 was confirmed and the interaction inhibited Pin1 PPIase activity. In addition, proliferation of cells expressing Pin1was inhibited and tumorgrowth in a xenograftmousemodel was suppressed. The binding of EGCGwith Arg17 in the WW domain prevented the binding of c-Jun, a well-known Pin1 substrate. EGCG treatment corresponded with a decreased abundance of cyclin D1 and diminution of 12-O-tetradecanoylphorbol-l3-acetate- induced AP-1 or NF-κB promoter activity in cells expressing Pin1. Overall, these results showed that EGCG directly suppresses the tumor-promoting effect of Pin1.

Original language	English
Pages (from-to)	1366-1377
Number of pages	12
Journal	Cancer Prevention Research
Volume	4
Issue number	9
DOIs	https://doi.org/10.1158/1940-6207.CAPR-11-0301
State	Published - Sep 2011

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title = "Epigallocatechin-gallate suppresses tumorigenesis by directly targeting Pin1",

abstract = "The most active anticancer component in green tea is epigallocatechin-3- gallate (EGCG). The human peptidyl prolyl cis/trans isomerase (Pin1) plays a critical role in oncogenic signaling. Herein, we report the X-ray crystal structure of the Pin1/EGCGcomplex resolved at 1.9{\AA} resolution.Notably, the structure revealed the presence of EGCG in both the WWand PPIase domains of Pin1. The direct binding of EGCG with Pin1 was confirmed and the interaction inhibited Pin1 PPIase activity. In addition, proliferation of cells expressing Pin1was inhibited and tumorgrowth in a xenograftmousemodel was suppressed. The binding of EGCGwith Arg17 in the WW domain prevented the binding of c-Jun, a well-known Pin1 substrate. EGCG treatment corresponded with a decreased abundance of cyclin D1 and diminution of 12-O-tetradecanoylphorbol-l3-acetate- induced AP-1 or NF-κB promoter activity in cells expressing Pin1. Overall, these results showed that EGCG directly suppresses the tumor-promoting effect of Pin1.",

author = "Urusova, {Darya V.} and Shim, {Jung Hyun} and Kim, {Dong Joon} and Jung, {Sung Keun} and Zykova, {Tatyana A.} and Andria Carper and Bode, {Ann M.} and Zigang Dong",

year = "2011",

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doi = "10.1158/1940-6207.CAPR-11-0301",

language = "English",

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AU - Urusova, Darya V.

AU - Shim, Jung Hyun

AU - Kim, Dong Joon

AU - Jung, Sung Keun

AU - Zykova, Tatyana A.

AU - Carper, Andria

AU - Bode, Ann M.

AU - Dong, Zigang

PY - 2011/9

Y1 - 2011/9

N2 - The most active anticancer component in green tea is epigallocatechin-3- gallate (EGCG). The human peptidyl prolyl cis/trans isomerase (Pin1) plays a critical role in oncogenic signaling. Herein, we report the X-ray crystal structure of the Pin1/EGCGcomplex resolved at 1.9Å resolution.Notably, the structure revealed the presence of EGCG in both the WWand PPIase domains of Pin1. The direct binding of EGCG with Pin1 was confirmed and the interaction inhibited Pin1 PPIase activity. In addition, proliferation of cells expressing Pin1was inhibited and tumorgrowth in a xenograftmousemodel was suppressed. The binding of EGCGwith Arg17 in the WW domain prevented the binding of c-Jun, a well-known Pin1 substrate. EGCG treatment corresponded with a decreased abundance of cyclin D1 and diminution of 12-O-tetradecanoylphorbol-l3-acetate- induced AP-1 or NF-κB promoter activity in cells expressing Pin1. Overall, these results showed that EGCG directly suppresses the tumor-promoting effect of Pin1.

AB - The most active anticancer component in green tea is epigallocatechin-3- gallate (EGCG). The human peptidyl prolyl cis/trans isomerase (Pin1) plays a critical role in oncogenic signaling. Herein, we report the X-ray crystal structure of the Pin1/EGCGcomplex resolved at 1.9Å resolution.Notably, the structure revealed the presence of EGCG in both the WWand PPIase domains of Pin1. The direct binding of EGCG with Pin1 was confirmed and the interaction inhibited Pin1 PPIase activity. In addition, proliferation of cells expressing Pin1was inhibited and tumorgrowth in a xenograftmousemodel was suppressed. The binding of EGCGwith Arg17 in the WW domain prevented the binding of c-Jun, a well-known Pin1 substrate. EGCG treatment corresponded with a decreased abundance of cyclin D1 and diminution of 12-O-tetradecanoylphorbol-l3-acetate- induced AP-1 or NF-κB promoter activity in cells expressing Pin1. Overall, these results showed that EGCG directly suppresses the tumor-promoting effect of Pin1.

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AN - SCOPUS:80052566095

SN - 1940-6207

VL - 4

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JO - Cancer Prevention Research

JF - Cancer Prevention Research

IS - 9

ER -

Epigallocatechin-gallate suppresses tumorigenesis by directly targeting Pin1

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