Green tea extract reduces induction of p53 and apoptosis in UVB-irradiated human skin independent of transcriptional controls.
Ultraviolet (UV) irradiation plays a pivotal role in human skin carcinongenesis. Preclinically, systemically and topically applied green tea extract (GTE) has shown reduction of UV-induced (i) erythema, (ii) DNA damage, (iii) formation of radical oxygen species and (iv) downregulation of numerous factors related to apoptosis, inflammation, differentiation and carcinogenesis. In humans, topical GTE has so far only been tested in limited studies, with usually very high GTE concentrations and over short periods of time. Both chemical stability of GTE and staining properties of highly concentrated green tea polyphenols limit the usability of highly concentrated green tea extracts in cosmetic products. The present study tested the utility of stabilized low-dose GTE as photochemopreventive agents under everyday conditions. We irradiated with up to 100 mJ/cm(2) of UVB light skin patches which were pretreated with either OM24-containing lotion or a placebo lotion. Biopsies were taken from both irradiated and un-irradiated skin for both immunohistochemistry and DNA microarray analysis. We found that while OM24 treatment did not significantly affect UV-induced erythema and thymidine dimer formation, OM24 treatment significantly reduced UV-induced p53 expression in keratinocytes. We also found that OM24 treatment significantly reduced the number of apoptotic keratinocytes (sunburn cells and TUNEL-positive cells). Carefully controlled DNA microarray analyses showed that OM24 treatment does not induce off-target changes in gene expression, reducing the likelihood of unwanted side-effects. Topical GTE (OM24) reduces UVB-mediated epithelial damage already at low, cosmetically usable concentrations, without tachyphylaxis over 5 weeks, suggesting GTE as suitable everyday photochemopreventive agents.
Mnich
Christian D
CD
Department of Dermatology, University Hospital of Zurich, Zurich, Switzerland.
Hoek
Keith S
KS
Virkki
Leila V
LV
Farkas
Arpad
A
Dudli
Christa
C
Laine
Elisabeth
E
Urosevic
Mirjana
M
Dummer
Reinhard
R
D000328:Adult; D000368:Aged; D017209:Apoptosis; D001706:Biopsy; D004249:DNA Damage; D005260:Female; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D012867:Skin / Q000378:metabolism*; D013662:Tea; D014158:Transcription, Genetic; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis / Q000378:metabolism*; D014466:Ultraviolet Rays
C495901:TP53 protein, human; D013662:Tea; D016159:Tumor Suppressor Protein p53