The multifaceted role of sulforaphane in protection against uv radiation-mediated skin damage

Ultraviolet radiation (UVR), the most abundant carcinogen in our environment, is the major factor in the etiology of skin damage and photocarcinogenesis. Common preventive measures, such as sunscreens and general sun avoidance, are not sufficiently effective, and skin cancer is the most common human cancer. Furthermore, cutaneous squamous cell carcinomas are among the most highly mutated human malignancies, carrying 1 mutation per ~30,000 bp of coding sequence. Such extraordinary mutation highlights the need for agents capable of affecting multiple hallmarks of cancer. UVR causes direct DNA damage, generation of reactive oxygen species (ROS), inflammation, and immunosuppression. These deleterious biological insults are counteracted by an elaborate network of cellular defense mechanisms. The isothiocyanate sulforaphane is a potent inducer of these defenses, which include cytoprotective antioxidant and antiinflammatory enzymes and glutathione. Sulforaphane-containing broccoli sprout extracts, administered either topically or in the diet, protect SKH-1 hairless mice against UVRmediated skin damage and tumor formation. In humans, application of these extracts to the skin of healthy subjects reduces susceptibility to erythema arising from acute exposure to UVR. Many of the protective effects of sulforaphane are due to the potent ability of the isothiocyanate to activate transcription factor Nrf2, and are lost in cells and animals that are Nrf2-deficient. In addition, sulforaphane provides Nrf2-independent protection, such as suppression of NFkB signaling and direct inhibition of the activity of macrophage migration inhibitory factor (MIF), a pro-inflammatory cytokine implicated in UVR-mediated skin damage and carcinogenesis. Thus, sulforaphane provides a paradigm for a dietary small molecule indirect antioxidant which plays a multifaceted role in protection against the damaging effects of oxidative stress and inflammation.