Document Detail


Effects of the isoflavone 4',5,7-trihydroxyisoflavone (genistein) on psoralen plus ultraviolet A radiation (PUVA)-induced photodamage.
MedLine Citation:
PMID:  11872639     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Long-term psoralen plus ultraviolet A radiation (PUVA) therapy is associated with an increased risk of squamous cell carcinoma and malignant melanoma. Genistein (4',5,7-trihydroxyisoflavone), a major isoflavone in soybeans and a specific inhibitor of protein tyrosine kinase, has been shown to inhibit UVB induced skin carcinogenesis in hairless mice. For this study we examined the protective effects of topical genistein on PUVA-induced photodamage. In two separate experiments, genistein in a dimethyl sulfoxide/acetone (1:9) solution was applied to SKH-1 female mice 1 h post 8-methoxy-psoralen dosing and 1 h prior to UVA irradiation. Application of genistein significantly decreased PUVA-induced skin thickening, and greatly diminished cutaneous erythema and ulceration in a dose-dependent manner. Histological examination showed that PUVA treatment of mouse skin induced dramatic inflammatory changes throughout the epidermis; topical genistein prevented these changes without noticeable adverse effects. Cells containing cleaved poly(ADP-ribose) polymerase (PARP) and active caspase-3 were significantly increased in PUVA-treated skin (P < 0.05 and P < 0.0001, respectively) as compared with unexposed control skin. Topical genistein completely inhibited cleavage of PARP and caspase-3. Proliferating cell nuclear antigen (PCNA) positive cells were observed in suprabasal areas of the epidermis and were significantly decreased in PUVA-treated skin compared with both control samples and samples treated with PUVA plus topical genistein (P < 0.005). These results indicate that genistein protects the skin from PUVA-induced photodamage.
Authors:
Eileen Q Shyong; Yuhun Lu; Alison Lazinsky; Rao N Saladi; Robert G Phelps; Lisa M Austin; Mark Lebwohl; Huachen Wei
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Carcinogenesis     Volume:  23     ISSN:  0143-3334     ISO Abbreviation:  Carcinogenesis     Publication Date:  2002 Feb 
Date Detail:
Created Date:  2002-03-01     Completed Date:  2002-04-04     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  8008055     Medline TA:  Carcinogenesis     Country:  England    
Other Details:
Languages:  eng     Pagination:  317-21     Citation Subset:  IM    
Affiliation:
Department of Dermatology, Mount Sinai School of Medicine, 1425 Madison Avenue, New York, NY 10029, USA.
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MeSH Terms
Descriptor/Qualifier:
Acetone / chemistry
Animals
Anticarcinogenic Agents / pharmacology
Caspase 3
Caspases / biosynthesis
DNA / radiation effects*
DNA Damage* / drug effects*,  radiation effects
Dimethyl Sulfoxide / pharmacology
Epidermis / metabolism
Female
Ficusin / pharmacology*
Genistein / pharmacology*
Immunohistochemistry
Mice
Models, Biological
Neoplasms, Radiation-Induced / prevention & control
Poly(ADP-ribose) Polymerases / metabolism
Proliferating Cell Nuclear Antigen / biosynthesis
Skin / drug effects
Time Factors
Ultraviolet Rays*
Grant Support
ID/Acronym/Agency:
R01CA85360/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Anticarcinogenic Agents; 0/Proliferating Cell Nuclear Antigen; 446-72-0/Genistein; 66-97-7/Ficusin; 67-64-1/Acetone; 67-68-5/Dimethyl Sulfoxide; 9007-49-2/DNA; EC 2.4.2.30/Poly(ADP-ribose) Polymerases; EC 3.4.22.-/Casp3 protein, mouse; EC 3.4.22.-/Caspase 3; EC 3.4.22.-/Caspases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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