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Epigallocatechin gallate inhibits phorbol ester-induced activation of NF-kappa B and CREB in mouse skin: role of p38 MAPK.
Ann N Y Acad Sci. 2007 Jan; 1095:504-12.AN

Abstract

The modulation of intracellular signaling network involved in an inappropriate expression of cyclooxygenase-2 (COX-2) is a pragmatic approach for chemoprevention with a wide variety of dietary phytochemicals. Epigallocatechin gallate (EGCG), a major green tea polyphenol, is one of the most extensively investigated chemopreventive agents. Our previous study revealed that EGCG inhibited expression of COX-2 and activation of mitogen-activated protein kinases (MAPKs) in mouse skin stimulated with a prototype tumor promotor 12-O-tetradecanoylphorbol-13-acetate (TPA). This study was aimed at identifying transcription factors as molecular targets of EGCG in downregulating COX-2 expression. We found that EGCG inhibited TPA-induced DNA binding of NF-kappaB and CREB in mouse skin in vivo. EGCG also suppressed TPA-induced phosphorylation and subsequent degradation of IkappaBalpha, and prevented nuclear translocation of p65. We also examined whether extracellular signal-regulated protein kinase (ERK) and p38 MAPK, which are known to regulate activation of NF-kappaB, can also modulate CREB DNA binding. Pretreatment with U0126 and SB203580, pharmacological inhibitors of ERK and p38 MAPK, respectively, showed that SB203580, but not U0126, attenuated TPA-induced CREB DNA binding in mouse skin. Taken together, EGCG inhibited TPA-induced DNA binding of NF-kappaB and CREB by blocking activation of p38 MAPK, which may provide a molecular basis of COX-2 inhibition by EGCG in mouse skin in vivo.

Authors+Show Affiliations

College of Pharmacy, Seoul National University, Shillim-dong, Kwanak-ku, Seoul 151-742, Korea.No affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17404063

Citation

Kundu, Joydeb Kumar, and Young-Joon Surh. "Epigallocatechin Gallate Inhibits Phorbol Ester-induced Activation of NF-kappa B and CREB in Mouse Skin: Role of P38 MAPK." Annals of the New York Academy of Sciences, vol. 1095, 2007, pp. 504-12.
Kundu JK, Surh YJ. Epigallocatechin gallate inhibits phorbol ester-induced activation of NF-kappa B and CREB in mouse skin: role of p38 MAPK. Ann N Y Acad Sci. 2007;1095:504-12.
Kundu, J. K., & Surh, Y. J. (2007). Epigallocatechin gallate inhibits phorbol ester-induced activation of NF-kappa B and CREB in mouse skin: role of p38 MAPK. Annals of the New York Academy of Sciences, 1095, 504-12.
Kundu JK, Surh YJ. Epigallocatechin Gallate Inhibits Phorbol Ester-induced Activation of NF-kappa B and CREB in Mouse Skin: Role of P38 MAPK. Ann N Y Acad Sci. 2007;1095:504-12. PubMed PMID: 17404063.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Epigallocatechin gallate inhibits phorbol ester-induced activation of NF-kappa B and CREB in mouse skin: role of p38 MAPK. AU - Kundu,Joydeb Kumar, AU - Surh,Young-Joon, PY - 2007/4/4/pubmed PY - 2007/5/9/medline PY - 2007/4/4/entrez SP - 504 EP - 12 JF - Annals of the New York Academy of Sciences JO - Ann N Y Acad Sci VL - 1095 N2 - The modulation of intracellular signaling network involved in an inappropriate expression of cyclooxygenase-2 (COX-2) is a pragmatic approach for chemoprevention with a wide variety of dietary phytochemicals. Epigallocatechin gallate (EGCG), a major green tea polyphenol, is one of the most extensively investigated chemopreventive agents. Our previous study revealed that EGCG inhibited expression of COX-2 and activation of mitogen-activated protein kinases (MAPKs) in mouse skin stimulated with a prototype tumor promotor 12-O-tetradecanoylphorbol-13-acetate (TPA). This study was aimed at identifying transcription factors as molecular targets of EGCG in downregulating COX-2 expression. We found that EGCG inhibited TPA-induced DNA binding of NF-kappaB and CREB in mouse skin in vivo. EGCG also suppressed TPA-induced phosphorylation and subsequent degradation of IkappaBalpha, and prevented nuclear translocation of p65. We also examined whether extracellular signal-regulated protein kinase (ERK) and p38 MAPK, which are known to regulate activation of NF-kappaB, can also modulate CREB DNA binding. Pretreatment with U0126 and SB203580, pharmacological inhibitors of ERK and p38 MAPK, respectively, showed that SB203580, but not U0126, attenuated TPA-induced CREB DNA binding in mouse skin. Taken together, EGCG inhibited TPA-induced DNA binding of NF-kappaB and CREB by blocking activation of p38 MAPK, which may provide a molecular basis of COX-2 inhibition by EGCG in mouse skin in vivo. SN - 0077-8923 UR - https://www.unboundmedicine.com/medline/citation/17404063/Epigallocatechin_gallate_inhibits_phorbol_ester_induced_activation_of_NF_kappa_B_and_CREB_in_mouse_skin:_role_of_p38_MAPK_ DB - PRIME DP - Unbound Medicine ER -