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The Multifaceted Role of Sulforaphane in Protection against UV Radiation-Mediated Skin Damage (pp. 185-208) $100.00
Authors:  (Andrea L. Benedict, Elena V. Knatko, Rumen V. Kostov, Ying Zhang, Maureen Higgins, Sukirti Kalra, Jed W. Fahey, Sally H. Ibbotson, Charlotte M. Proby, Paul Talalay and Albena T. Dinkova-Kostova, Lewis B. and Dorothy Cullman Chemoprotection Center, Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA)
Abstract:
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
burden makes the possibility for success of a single-target therapy questionable and
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 NFκB 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. 


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The Multifaceted Role of Sulforaphane in Protection against UV Radiation-Mediated Skin Damage (pp. 185-208)