Our interest in the natural product sulforaphane (SF) began with studies of patients at high risk for melanoma. Germline loss-of-function (LOF) mutations in the highly polymorphic melanocortin-1 receptor gene (MC1R), confers a 4-fold increased risk for melanoma. Much of this increase arises from the loss of MC1R-mediated upregulation of antioxidant, pigment synthesis, DNA repair and anti-apoptotic pathways that protect epidermal melanocytes from the mutagenic effects of UV radiation. We have found that SF (likely due to its antioxidant activity) protects both normal human melanocytes, and the skin of human subjects with LOF MC1R mutations, from the harmful effects of UV light. Shave biopsies were harvested from donors with either wild-type MC1R or two LOF alleles. The epidermal tissues were treated ex vivo with UV and/or SF then analyzed histologically and by qPCR. Our results showed that SF provides significant protection from UV to both melanocytes and skin. We found also that the antioxidant protein thioredoxin reductase 1 (TR1) was significantly induced by SF. In order to explore the role of TR1 in protecting melanocytes from UV-induced damage, we have created a human melanocyte cell line that expresses a micro RNA which targets TR1. These cells display increased sensitivity to the effects of UV and differential processing of the pigment synthesis protein tyrosinase. This study demonstrates the promise of SF as an agent for protection of human skin in individuals with high-risk MC1R genotypes from the effects of UV light, and highlights the role of TR1 in this process.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1593. doi:1538-7445.AM2012-1593