RT Journal Article
SR Electronic
T1 Green Tea Polyphenol-Induced Epidermal Keratinocyte Differentiation Is Associated with Coordinated Expression of p57/KIP2 and Caspase 14
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 884
OP 890
DO 10.1124/jpet.104.076075
VO 312
IS 3
A1 Stephen Hsu
A1 Tetsuya Yamamoto
A1 James Borke
A1 Douglas S. Walsh
A1 Baldev Singh
A1 Sushma Rao
A1 Kamatani Takaaki
A1 Nam Nah-Do
A1 Carol Lapp
A1 David Lapp
A1 Emily Foster
A1 Wendy B. Bollag
A1 Jill Lewis
A1 John Wataha
A1 Tokio Osaki
A1 George Schuster
YR 2005
UL http://jpet.aspetjournals.org/content/312/3/884.abstract
AB Epigallocatechin-3-gallate (EGCG), the most abundant polyphenol in green tea, exerts chemopreventive effects by selectively inducing apoptosis in tumor cells. In contrast, EGCG accelerates terminal differentiation in normal human epidermal keratinocytes (NHEK) mediated partially by up-regulation of p57/KIP2, a cyclin-dependent kinase inhibitor that confers growth arrest and differentiation. However, it is unclear if EGCG modulates caspase 14, a unique regulator of epithelial cell terminal differentiation associated with cornification. Here, we examined the effect of EGCG on caspase 14 expression in NHEK and correlated the protein and mRNA expression of p57/KIP2 with those of caspase 14 in either normal keratinocytes or p57/KIP2-expressing tumor cells (OSC2, an oral squamous cell carcinoma cell line). Additionally, paraffin-embedded normal and untreated psoriatic (aberrant keratinization) skin sections from humans were assessed for caspase 14 by immunohistochemistry. In NHEK, EGCG induced the expression of caspase 14 mRNA and protein levels within a 24-h period. The expression of p57/KIP2 in OSC2 cells was adequate to induce caspase 14 in the absence of EGCG; this induction of caspase 14 was down-regulated by transforming growth factor-β1. In human psoriatic skin samples, caspase 14 staining in the upper epidermis was reduced, especially in nuclear areas. These results suggest that, in addition to p57/KIP2, EGCG-induced terminal differentiation of epidermal keratinocytes involves up-regulation of caspase 14. Further understanding of how EGCG modulates cellular differentiation may be useful in developing green tea preparations for selected clinical applications. The American Society for Pharmacology and Experimental Therapeutics