title: Effects of the isoflavone 4',5,7-trihydroxyisoflavone (genistein) on psoralen plus ultraviolet A radiation (PUVA)-induced photodamage.
abstract: 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.affiliation: Department of Dermatology, Mount Sinai School of Medicine, 1425 Madison Avenue, New York, NY 10029, USA.
authors.forename: Eileen Q
authors.initials: EQ
authors.lastname: Shyong
authors.forename: Yuhun
authors.initials: Y
authors.lastname: Lu
authors.forename: Alison
authors.initials: A
authors.lastname: Lazinsky
authors.forename: Rao N
authors.initials: RN
authors.lastname: Saladi
authors.forename: Robert G
authors.initials: RG
authors.lastname: Phelps
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Austin
authors.forename: Mark
authors.initials: M
authors.lastname: Lebwohl
authors.forename: Huachen
authors.initials: H
authors.lastname: Wei
mesh_terms: D000096:Acetone / Q000737:chemistry; D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology; D053148:Caspase 3; D020169:Caspases / Q000096:biosynthesis; D004247:DNA / Q000528:radiation effects*; D004249:DNA Damage / Q000187:drug effects* / Q000528:radiation effects; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D004817:Epidermis / Q000378:metabolism; D005260:Female; D005363:Ficusin / Q000494:pharmacology*; D019833:Genistein / Q000494:pharmacology*; D007150:Immunohistochemistry; D051379:Mice; D008954:Models, Biological; D009381:Neoplasms, Radiation-Induced / Q000517:prevention & control; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D018809:Proliferating Cell Nuclear Antigen / Q000096:biosynthesis; D012867:Skin / Q000187:drug effects; D013997:Time Factors; D014466:Ultraviolet Rays
chemical_list: D016588:Anticarcinogenic Agents; D018809:Proliferating Cell Nuclear Antigen; D000096:Acetone; D004247:DNA; D019833:Genistein; D011065:Poly(ADP-ribose) Polymerases; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases; D005363:Ficusin; D004121:Dimethyl Sulfoxide