(-)-Epigallocatechin-3-gallate inhibition of ultraviolet B-induced AP-1 activity

Barthelman, M.; Bair, Warner B.; Stickland, Kimberly; Chen, Weixing; Timmermann, Barbara N.; Valcic, Susanne; Dong, Zigang; Bowden, G. Timothy

doi:10.1093/carcin/19.12.2201

Cited by 130 publications

(73 citation statements)

References 24 publications

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“…Previously, we have shown that EGCG, a polyphenol compound isolated from green tea, not only decreased UVB induced AP-1 activation and c-fos expression, but also inhibited UVB induced p38 activation in human keratinocytes (Barthelman et al, 1998b;Chen et al, 1999b). These results implied that the mechanism of EGCG inhibition of UVB induced AP-1 activation and c-fos expression might be through inhibition of p38 activation.…”

Section: Discussionmentioning

confidence: 69%

“…These results indicated that c-fos expression might play a key role in UVB induced AP-1 activation in human keratinocytes. (7)-Epigallocatechin gallate (EGCG), a chemoprevention agent isolated from green tea, inhibited UVB induced c-fos gene expression and AP-1 activation (Chen et al, 1999b;Barthelman et al, 1998b). It appears that c-fos could be a target gene for chemoprevention of skin cancer.…”

Section: Introductionmentioning

confidence: 99%

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Activation of p38 MAP kinase and ERK are required for ultraviolet-B induced c-fos gene expression in human keratinocytes

Chen

Bowden

1999

Oncogene

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The e ects of p38 MAP kinase and ERK on UVB induced c-fos gene expression were studied in a human keratinocyte cell line, FL30. UVB signi®cantly increased c-fos gene expression at both the transcriptional and protein levels. p38 and ERK were also signi®cantly activated after UVB irradiation. Treating the cells with p38 inhibitor SB202190 inhibited p38 activation, but not ERK; treating the cells with MEK-1 inhibitor PD98059 inhibited ERK activation without suppressing p38 activation. The kinase activation was determined by Western blots using phospho-p38 or ERK antibodies, or an in vivo p38 activity assay. Further studies demonstrated that blocking p38 almost completely abrogated UVB induced c-fos gene transcription and c-Fos protein synthesis. Inhibiting ERK partially abrogated UVB induced c-fos transcriptional and protein levels. Suppression of both p38 and ERK not only completely blocked UVB induced c-fos expression, but also decreased c-fos gene basal expression. Our data indicated that p38 may play a more important role than ERK in UVB induced cfos expression in human keratinocytes. Since c-fos expression may play an important role in UVB induced AP-1 activation, and AP-1 activation is known to play a role in tumor promotion, both p38 and ERK could be potential targets for chemoprevention of skin cancer.

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Section: Discussionmentioning

confidence: 69%

Section: Introductionmentioning

confidence: 99%

Activation of p38 MAP kinase and ERK are required for ultraviolet-B induced c-fos gene expression in human keratinocytes

Chen

Bowden

1999

Oncogene

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“…(n ϭ 3). scription factors, including NFB (43,44), c-fos (45,46), junB, junD and Fra-1 (8), and signal transducers and activators of transcription (STAT) (47), the present study is the first to define C/EBP as a target. The findings from our present study, when considered with our previous study (8), suggests that EGCG triggers a Ras, MEKK1, MEK3, p38␦ cascade that, in turn, increases C/EBP factor level and increases complex formation on the hINV promoter C/EBP site.…”

Section: Fig 6 Curcumin Inhibits Carasand Mekk1-dependent Hinv Prommentioning

confidence: 85%

Green Tea Polyphenol and Curcumin Inversely Regulate Human Involucrin Promoter Activity via Opposing Effects on CCAAT/Enhancer-binding Protein Function

Balasubramanian¹,

Eckert

2004

Journal of Biological Chemistry

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Antioxidants are important candidate agents for the prevention of disease. However, the possibility that different antioxidants may produce opposing effects in tissues has not been adequately explored. We have reported previously that (؊)-epigallocatechin-3-gallate (EGCG), a green tea polyphenol antioxidant, stimulates expression of the keratinocyte differentiation marker, involucrin (hINV), via a Ras, MEKK1, MEK3, p38␦ signaling cascade (Balasubramanian, S., Efimova, T., and Eckert, R. L. (2002) J. Biol. Chem. 277, 1828 -1836). We now show that EGCG activation of this pathway results in increased CCAAT/enhancer-binding protein (C/EBP␣ and C/EBP␤) factor level and increased complex formation at the hINV promoter C/EBP DNA binding site. This binding is associated with increased promoter activity. Mutation of the hINV promoter C/EBP binding site eliminates the regulation as does expression of GADD153, a dominant-negative C/EBP factor. In contrast, a second antioxidant, curcumin, inhibits the EGCG-dependent promoter activation. This is associated with inhibition of the EGCG-dependent increase in C/EBP factor level and C/EBP factor binding to the hINV promoter. Curcumin also inhibits the EGCG-dependent increase in endogenous hINV levels. The curcumin-dependent suppression of C/EBP factor level is inhibited by treatment with the proteasome inhibitor MG132, suggesting that the proteasome function is required for curcumin action. We conclude that curcumin and EGCG produce opposing effects on involucrin gene expression via regulation of C/EBP factor function. The observation that two antioxidants can produce opposite effects is an important consideration in the context of therapeutic antioxidant use.

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“…Third, chemopreventive agents can produce different responses in normal versus immortalized/transformed keratinocytes. Thus, in normal keratinocytes EGCG increases AP1 factor levels, while in immortalized/transformed keratinocytes EGCG treatment reduces AP1 factor expression (Nomura et al, 2000;Dong et al, 1997;Barthelman et al, 1998;Chung et al, 1999). This suggests that the activity and mechanism of chemopreventive agent action may change during disease progression.…”

Section: Discussionmentioning

confidence: 99%

Keratinocyte proliferation, differentiation, and apoptosis—Differential mechanisms of regulation by curcumin, EGCG and apigenin

Balasubramanian

Eckert

2007

Toxicology and Applied Pharmacology

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We have proposed that it is important to examine the impact of chemopreventive agents on the function of normal human epidermal keratinocytes, since these cells comprise the barrier that protects the body from a range of environmental insults. In this context, it is widely appreciated that cancer may be retarded by consumption or topical application of naturally-occurring food-derived chemopreventive agents. Our studies show that (−)-epigallocatechin-3-gallate (EGCG), a green teaderived polyphenol, acts to enhance the differentiation of normal human keratinocytes as evidenced by its ability to increase involucrin (hINV), transglutaminase type 1 (TG1) and caspase-14 gene expression. EGCG also stimulates keratinocyte morphological differentiation. These actions of EGCG are mediated via activation of a nPKC, Ras, MEKK1, MEK3, p38δ-ERK1/2 signaling cascade which leads to increased activator protein 1 (AP1) and CAATT enhancer binding protein (C/EBP) transcription factor expression, increased binding of these factors to DNA, and increased gene transcription. In contrast, apigenin, a dietary flavonoid derived from plants and vegetables, and curcumin, an agent derived from turmeric, inhibit differentiation by suppressing MAPK signal transduction and reducing API transcription factor level. Curcumin also acts to enhance apoptosis, although EGCG and apigenin do not stimulate apoptosis. In addition, all of these agents inhibit keratinocyte proliferation. These findings indicate that each of these diet-derived chemopreventive agents has a profound impact on normal human keratinocyte function and that they operate via distinct and sometimes opposing mechanisms. However, all are expected to act as chemopreventive agents. KeywordsEGCG; apigenin; curcumin; TPA; epidermis; involucrin; keratinocyte differentiation; apoptosis; chemoprevention; turmeric Keratinocyte differentiation and human involucrin gene expressionThe keratinocyte is the major cell type of the multilayered stratified squamous epithelium (the epidermis) that covers the body surface. To establish epidermal structure, keratinocytes in the basal layer undergo periodic cell division which gives rise to daughter cells that differentiate

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(-)-Epigallocatechin-3-gallate inhibition of ultraviolet B-induced AP-1 activity

Cited by 130 publications

References 24 publications

Activation of p38 MAP kinase and ERK are required for ultraviolet-B induced c-fos gene expression in human keratinocytes

Activation of p38 MAP kinase and ERK are required for ultraviolet-B induced c-fos gene expression in human keratinocytes

Green Tea Polyphenol and Curcumin Inversely Regulate Human Involucrin Promoter Activity via Opposing Effects on CCAAT/Enhancer-binding Protein Function

Keratinocyte proliferation, differentiation, and apoptosis—Differential mechanisms of regulation by curcumin, EGCG and apigenin

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