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.

Platelet-Activating Factor Is Crucial in Psoralen and Ultraviolet A-Induced Immune Suppression, Inflammation, and Apoptosis

“…24 Moreover, the isoflavone genistein, a specific inhibitor of tyrosine kinase, has been shown to inhibit chemical carcinogeninduced reactive oxygen species and PUVA-induced photodamage, including inflammatory skin changes such as dermal neutrophilic and lymphocytic infiltration. 25 We observed that ex vivo PUVA-treated and UVAtreated PC but not unirradiated PC induced immune suppression in a dose-dependent manner (Figure 1c). Surprisingly however, there was no difference in the UVA dose response dependency or the UVA threshold dose for immune suppression, irrespective whether or not psoralen was added to the UVA-irradiated PC solution before UVA irradiation.…”

RETRACTED ARTICLE: Poly(Adenosine Diphosphate-Ribose) Polymerase-1 Expression in Cutaneous Malignant Melanomas as a New Molecular Marker of Aggressive Tumor

“…Recently, it has been reported that the inhibition of PARP-1 activity is a promising strategy to improve the outcome of cytotoxic therapies in different tumor models [17].…”

The role of estrogen deficiency in skin ageing and wound healing

“…Our recent studies indicate that the SERMs tamoxifen, raloxifene and genistein all substantially benefit healing in the estrogen-deprived Ovx mouse, promoting re-epithelialisation and contraction, and reducing inflammation, an effect that is most likely mediated via ERb (Emmerson et al 2010;Hardman et al 2008), while a separate study provides evidence that genistein accelerates murine healing by modulating TGFb1 (Marini et al 2010). Tamoxifen, raloxifene and genistein are anti-inflammatory in other pathologies, including systemic lupus erythematosus (SLE) (Sthoeger et al 2003), stroke (Tian et al 2009), UV-associated cutaneous damage (Brand and Jendrzejewski 2008;Shyong et al 2002;Widyarini et al 2001), colitis (Seibel et al 2009), ileitis (Sadowska-Krowicka et al 1998) and multiple sclerosis (MS) (De Paula et al 2008). An important and on-going goal of our research is to evaluate cutaneous healing in post-menopausal women prescribed topical SERM treatment.…”