Changing skin pigmentation may prevent UV cancer – Harvard Gazette

A skin pigmentation mechanism that can darken human skin color as a natural defense against ultraviolet (UV)-associated cancers has been discovered by scientists at Harvard-affiliated Massachusetts General Hospital (MGH). Mediating the biological process is an enzyme called nicotinamide nucleotide transhydrogenase (NNT), which plays a key role in the production of melanin (a pigment that protects the skin from harmful UV rays. Its inhibition by a topical medication or ointment could potentially reduce the risk of skin cancer, as presented in a study in Cell.

“Skin pigmentation and its regulation are of crucial importance because the pigments confer major protection against UV-related skin cancers, which are the most common malignant tumors in humans”, explains David Fisher, main author and co-correspondent, head of the dermatology department. at the MGH. “People with darker pigmentation are better protected against carcinogenic UV rays by the light scattering and antioxidant properties of melanin, while people with fairer and fairer skin are the most vulnerable. risk of developing skin cancer. “

Through their lab work with the skin of humans and animal models, MGH researchers mimicked the natural protection that exists in people with dark pigments. In the process, they gained a better understanding of the biochemical mechanism involved, as well as their drivers and how they might be influenced by a topical agent independent of UV radiation, sun exposure, or genetics.

“We speculated that the enzymes that make melanin by oxidizing the amino acid tyrosine in the melanosome (the synthesis and storage compartment of the cell) are largely regulated by gene expression,” says Fisher. They were surprised to learn, however, that the amount of melanin produced is largely regulated by a very different chemical mechanism, which can ultimately be attributed to NNT in the mitochondria, the internal chamber of the cell, with the ability to alter skin pigmentation.

The researchers found that topical application of small molecule inhibitors of NNT resulted in darkening of human skin and that mice with reduced NNT function exhibited increased pigmentation of the fur. To test their discovery, they tested the skin with UV rays and found that skin with darker pigments was indeed protected from DNA damage inflicted by ultraviolet rays.

“We are excited about the discovery of a distinct pigmentation mechanism, as it could pave the way, after further studies and safety evaluations, for a new approach to darkening and skin protection by targeting the NNT ”, says Elisabeth Roider, former researcher at MGH. , and lead author and co-author of the study. “The overarching goal, of course, is to improve skin cancer prevention strategies and to offer new, effective treatment options to the millions of people with pigment disorders.”

Fisher is professor of dermatology and pediatrics at Harvard Medical School and director of the Cutaneous Biology Research Center and the Melanoma Center at MGH. Roider is an attending physician in the Department of Dermatology at the University Hospital of Basel, Switzerland, and a visiting scientist at the MGH Skin Biology Research Center.