Applied as a cream to the skin, the drug allowed red-haired mice to develop a deep tan.
We worked with medicinal chemist Nathanael Gray to generate SIK inhibitors which could penetrate human skin.
"There is a limited number of drugs available that can effectively elevate pigmentation in a safe way", said Zippin, who was not involved with the new research. They stressed that further tests are needed to safeguard against potential side-effects in humans. One of their compounds made a brown splotch, indicating that it was able to reach the melanocytes in the skin and spur melanin production, the team reports today in Cell Reports. However, the researchers soon found that forskolin could not get into human skin. Because humans are relatively hairless compared to other mammals, our skin has had to toughen up, evolving to withstand a range of environment threats, such as ultraviolet radiation, muddy water, and cold temperatures. "We are talking about millions of young people potentially not using tanning beds each year. It's a different class of compounds, that work by targeting a different enzyme that converges on the same pathway that leads to pigmentation".
Fisher: Work from other scientists showed that the SIK kinase enzyme inhibits the MITF gene, which controls skin pigmentation. The Massachusetts General Hospital team anticipates that this discovery could stop skin cancer and even slow down the development of signs of aging.
The next step will be to determine whether the compounds are safe for human use. Now, they've figured out how to do the same in laboratory samples of human skin, inducing a tan exactly the same way the sun does. The tan lasted several days.
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In animal tests, red-haired mice became "almost jet black in a day or two with a strong enough dose", the researchers observed. The color fades away over time as normal skin cells slough off the surface, and skin tone gets back to normal within a week or so.
"Skin is the most common organ in our bodies to be afflicted with cancer, and the majority of cases are thought to be associated with UV radiation", he said.
"The potential importance of this study will ultimately lie in a new skin protection and skin cancer prevention strategy", Dr. Fisher said. "Our approach could help switch pigments to those found in darker skin, without a need for UV exposure". But we've found that the picture is more complicated, that red-blonde pigments are also more intrinsically carcinogenic, whereas dark melanin is intrinsically beneficial if not produced through use of unsafe UV injury to skin.
The long-term goal of this research is to create something that could be used in combination with traditional UV-absorbing sunscreens. The drug will still not appear on the shelves as the scientists want to do more safety testing.
This work was supported by the National Institutes of Health, the Melanoma Research Alliance, the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation, and the Canadian Institutes of Health Research.
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