Journal Article

Effects of the isoflavone 4′,5,7-trihydroxyisoflavone (genistein) on psoralen plus ultraviolet A radiation (PUVA)-induced photodamage

Eileen Q. Shyong, Yuhun Lu, Alison Lazinsky, Rao N. Saladi, Robert G. Phelps, Lisa M. Austin, Mark Lebwohl and Huachen Wei

in Carcinogenesis

Volume 23, issue 2, pages 317-321
Published in print February 2002 | ISSN: 0143-3334
Published online February 2002 | e-ISSN: 1460-2180 | DOI: https://dx.doi.org/10.1093/carcin/23.2.317
Effects of the isoflavone 4′,5,7-trihydroxyisoflavone (genistein) on psoralen plus ultraviolet A radiation (PUVA)-induced photodamage

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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.

Keywords: DMSO, dimethyl sulfoxide; genistein, 4′,5,7-trihydroxyisoflavone; 8-MOP, 8-methoxy-psoralen; PARP, poly(ADP-ribose) polymerase; PBS, phosphate-buffered saline; PCNA, proliferating cell nuclear antigen; PUVA, psoralen plus ultraviolet A radiation; UVA, ultraviolet A radiation

Journal Article.  3765 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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