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.

Cardiovascular diseases, osteoporosis-related hip fractures, and various cancers of the colon, prostate, uterus, and breast are remarkably less prevalent in Asia than in other industrialized countries. It is believed that the large consumption of soy products in Asian countries is contributory to the reduction of these chronic disorders. Genistein is a major isoflavone found in most soy products and plays an important role in the promotion of human health. Extensive epidemiological, in vitro, and animal studies have been performed, and most studies indicate that genistein has beneficial effects on a multitude of human disorders, including cancers, cardiovascular diseases, osteoporosis, and postmenopausal symptoms. To date, there is an abundance of promising studies supporting genistein's potential uses, but further research is still needed to validate its preventative and therapeutic efficacy. In addition, the adverse effects of genistein have drawn public attention. More studies are required to assess the potential detrimental effect of genistein, and a benefit-risk ratio should be considered before future clinical studies are performed.

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