Washington, D.C. -- The compound sulforaphane whose natural precursors are found at high levels in broccoli and other cruciferous vegetables has been hailed for its chemopreventive powers against cancer. Now sulforaphane has demonstrated new skills in treating a genetic skin blistering disorder called epidermolysis bullosa simplex (EBS), Pierre Coulombe and colleagues at the Johns Hopkins University School of Medicine in Baltimore report at the American Society for Cell Biology 47th Annual Meeting.
EBS is a rare but devastating inherited condition in which fluid-filled lesions called bullae appear at sites of frictional trauma to the skin. Unfortunately, treatment options for EBS are limited and palliative in nature. Much work remains to be done before sulforaphane can be tested clinically with EBS patients, but Coulombe notes that extracts from broccoli sprouts rich in sulforaphane have already been shown to be safe for use in human skin.
In EBS patients, the bottom layer of the epidermis, which is made of cells called keratinocytes, is unusually fragile and ruptures readily. Molecularly, most cases of EBS result from mutations in genes that produce the proteins keratin 5 (K5) and keratin 14 (K14). These proteins co-polymerize to form the intermediate filament cytoskeleton in basal keratinocytes. Since the discovery in 1991 that EBS is a keratin-based disease, more than 40 additional disorders affecting a broad range of tissues have been traced to defects in genes that encode intermediate filament proteins.
Coulombe and colleagues turned to sulforaphane in their search for a chemical activator that would induce the production of missing keratins in basal epidermis. There are 54 conserved keratin proteins in mammals -- meaning that evolution favored their survival. Many of these keratins are closely related in their genetic sequences and their properties and by their distribution within epithelial tissues. Coulombe reasoned that
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American Society for Cell Biology