Green tea polyphenol-induced epidermal keratinocyte differentiation is associated with coordinated expression of p57/KIP2 and caspase 14.
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-beta1. 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.
Hsu
Stephen
S
Department of Oral Biology and Maxillofacial Pathology, School of Dentistry, AD1443, Medical College of Georgia, Augusta, GA 30912-1126, USA. shsu@mail.mcg.edu
Yamamoto
Tetsuya
T
Borke
James
J
Walsh
Douglas S
DS
Singh
Baldev
B
Rao
Sushma
S
Takaaki
Kamatani
K
Nah-Do
Nam
N
Lapp
Carol
C
Lapp
David
D
Foster
Emily
E
Bollag
Wendy B
WB
Lewis
Jill
J
Wataha
John
J
Osaki
Tokio
T
Schuster
George
G
D053456:Caspase 14; D020169:Caspases / Q000032:analysis / Q000235:genetics*; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D050761:Cyclin-Dependent Kinase Inhibitor p57; D000078404:Epidermal Cells; D004817:Epidermis / Q000187:drug effects*; D005786:Gene Expression Regulation; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects*; D009687:Nuclear Proteins / Q000032:analysis / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis; D013662:Tea; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D053773:Transforming Growth Factor beta1
C493964:CDKN1C protein, human; D050761:Cyclin-Dependent Kinase Inhibitor p57; D009687:Nuclear Proteins; D012333:RNA, Messenger; C508960:TGFB1 protein, human; D013662:Tea; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D002392:Catechin; C045651:epigallocatechin gallate; C506446:CASP14 protein, human; D053456:Caspase 14; D020169:Caspases