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takyon writes:

Is your skin naturally toned from a UV tanning bed, or are you on salt-inducible kinase inhibitors?

A new compound promises to give human skin a suntan without the sun. The compound hasn't yet been tested in clinical trials—just in mice and on patches of human skin leftover from surgeries. But doctors are hopeful it could one day combat skin cancer by keeping people away from harmful ultraviolet (UV) rays.

"Assuming there are no safety concerns, it is clearly a better option than UV exposure," says Jerod Stapleton, a behavioral scientist at the Rutgers Cancer Institute of New Jersey in New Brunswick who studies indoor tanning and was not involved in the work. "We are talking about millions of young people potentially not using tanning beds each year. ... It could be a game-changer for skin cancer prevention."

The advance has its origins in a strain of "redhead" mice with rust-colored fur. The rodents harbor a variant of a gene called MC1R that gives rise to red hair and fair skin in humans. A properly functioning MC1R gene encodes a receptor that sits on the surface of skin cells called melanocytes, which transmit a signal to crank out dark melanin pigments; these pigments help protect skin cells from UV radiation. The redhead version of the receptor doesn't respond to the make-more-melanin signal, which explains why redheaded humans tend to burn, not tan.

David Fisher, a dermatologist at Massachusetts General Hospital in Boston, reasoned that he could help people tan by finding a way to stimulate this melaninmaking pathway. He and chemist Nathanael Gray of the Dana-Farber Cancer Institute in Boston targeted a protein called salt-inducible kinase (SIK), which works like a master off switch in the melanin factory. They bought a molecule known to inhibit SIK from a chemical supplier, and applied the compound as a liquid to the shaven backs of the redhead mice. After 7 days of daily treatment, the mouse skin turned "almost jet black," Fishers says. The tan was reversible though, and the rodents' skin tone returned mostly back to normal in about 2 weeks. Fisher notes that were no apparent safety concerns, but this would need to be tested more rigorously before human application.

A UV-Independent Topical Small-Molecule Approach for Melanin Production in Human Skin (open, DOI: 10.1016/j.celrep.2017.05.042) (DX)

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