Isoflavone Genistein: Photoprotection and Clinical Implications in Dermatology

Abstract

Genistein is a soybean isoflavone with diverse biological activities. It is a potent antioxidant, a specific inhibitor of protein tyrosine kinase, and a phytoestrogen. In recent years, increasing evidence has accumulated that this natural ingredient shows preventative and therapeutic effects for breast and prostate cancers, postmenopausal syndrome, osteoporosis, and cardiovascular diseases in animals and humans. In the past decade we have conducted a series of studies and demonstrated that genistein has significant antiphotocarcinogenic and antiphotoaging effects. Genistein substantially inhibits skin carcinogenesis and cutaneous aging induced by ultraviolet (UV) light in mice, and photodamage in humans. The mechanisms of action involve protection of oxidative and photodynamically damaged DNA, downregulation of UVB-activated signal transduction cascades, and antioxidant activities. In this article, we review the biological activities of genistein, as well as published and unpublished research from our laboratory. In addition, we discuss the potential application of genistein to clinical dermatology.

Multi-targeted therapy of cancer by genistein

“…Furthermore, genistein protects the skin from the effect of long-term psoralen plus ultraviolet A radiation (PUVA) therapy which is associated with an increased risk of squamous cell carcinoma and malignant melanoma [99; 100]. Additionally genistein is also reported to substantially inhibit skin carcinogenesis and cutaneous aging induced by ultraviolet (UV) light in mice [99]. In a murine PTEN (mPTEN) heterozygous (+/−) mutant mouse model for endometrial carcinoma, as well as in estrogenrelated endometrial carcinogenesis, genistein exerted an inhibitory effect on PTEN-related tumorigenesis [101].…”

Bioactive Food Components for Melanoma: An Overview

“…A dose-dependent inhibition of UVB-induced pyrimidine dimer formation was observed relative to increasing genistein concentrations [65]. Genistein substantially inhibits skin carcinogenesis and cutaneous aging induced by UV in mice and photodamage in humans [66]. Topical application of genistein before UVB radiation reduced the expression of c-fos and c-jun in the SENCAR mouse skin in a dose dependent manner [67].…”

Photoprotection of natural flavonoids

“…Genistein modulates photocarcinogenesis through enhancement of antioxidant enzyme activities and scavenging of oxygen free radicals (Wei et al, 1993;Giles et al, 1997), inhibition of UVR-induced oxidative DNA damage in purified DNA and culture cells (Wei et al, 1993;Wei et al, 1996;, suppression of UVR-induced protooncogene (c-fos and c-jun) expression in mouse epidermis and downregulation of UVR-activated phosphorylation of epidermal growth factorreceptor and tyrosine kinase activities . Genistein effectively blocks UVB-induced skin burns in humans as well as psoralen plus UVA (PUVA) induced photodamage and molecular alterations in hairless mouse skin (Wei et al, 2003;Shyong et al, 2002). The antipromotional of genistein activities are primarily associated with the anti-inflammatory pathways, down regulation of tyrosine protein kinase (TPK) activities, and expression of protooncogenes associated with cell proliferation (Wei et al, 2003).…”

“…Genistein effectively blocks UVB-induced skin burns in humans as well as psoralen plus UVA (PUVA) induced photodamage and molecular alterations in hairless mouse skin (Wei et al, 2003;Shyong et al, 2002). The antipromotional of genistein activities are primarily associated with the anti-inflammatory pathways, down regulation of tyrosine protein kinase (TPK) activities, and expression of protooncogenes associated with cell proliferation (Wei et al, 2003). Genistein also protected UVB-induced senescence-like characteristics in human dermal fibroblasts via maintenance of antioxidant enzyme activities and modulation of mitochondrial oxidative stress through down regulation of a p66Shc (the 66-kilodalton isoform of the growth factor adapter Shc) dependent signaling pathway (Wang et al, 2010).…”