Early drug tests show a boost in melanin without the sun
A method that gives mice a tan without using ultraviolet radiation now works in human skin samples. It’s an early step in developing a lotion or cream that might provide fair-skinned folk with protection against skin cancer.
As reported June 13 in Cell Reports, a topical drug penetrated and tanned laboratory samples of live human skin, absent the sun. Unlike self-tanning lotions that essentially stain skin brown and provide minimal sun protection, the drug activates the production of the dark form of the skin pigment melanin, which absorbs UV radiation and diminishes damage to skin cells.
The team behind this study had worked with a different drug, the plant extract forskolin, in a 2006 study. The researchers used mice with skin like that of red-haired, fair-skinned people, who don’t tan because of a nonfunctioning protein on the surface of the skin cells that make melanin. Applying forskolin to these mice stimulated production of the dark form of melanin. When exposed to UV rays, the mice with dark pigment had less DNA damage and sunburn, as well as fewer skin tumors, compared with untreated mice (SN: 9/23/06, p. 196).
“There was an obvious interest in asking, could this be applied to human skin?” says David Fisher, a cancer biologist at Massachusetts General Hospital in Boston. But the human epidermis, the outermost layer of skin, is about five times thicker in humans than in mice, he says, which means that many drugs “simply can’t get in.” Sure enough, this was true for forskolin.
So Fisher and colleagues looked at another way to activate pigmentation, focusing on a different enzyme than the one forskolin had targeted. Another research group had shown that an enzyme called salt-inducible kinase inhibits melanin production in mice and that animals lacking the gene for this enzyme developed darkened fur. This provided the opportunity to “try to target that inhibitor, block it and thereby stimulate pigmentation” with a drug, Fisher says.
The researchers tinkered with the structures of drugs to make them able to penetrate human skin while retaining their enzyme-blocking ability. In a liquid form applied to the skin, the best drug deeply tanned the human skin sample after eight days, with one treatment a day. Experiments in mice with a similar drug showed the tan faded after treatment ended.
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Even if a pigmentation-stimulating drug is found to be safe and effective in people, it would likely not be a substitute for sunscreen, Fisher says. Instead, the drug could be combined with sunscreen in a single product. He thinks the first test would be to see if this combination approach can protect against skin cancer in fair-skinned people or those with high sensitivity to sunlight.
“This is a very interesting new development of a potentially very useful product,” says Marianne Berwick, a molecular epidemiologist at the University of New Mexico School of Medicine in Albuquerque, who was not involved with the study. How useful the drug may be depends upon how well it actually lowers skin cancer risk and whether it is easy for people to use, she says.
“Humans are funny animals and do not necessarily do what is best for them,” Berwick says, such as applying sunscreen as frequently and thickly as directed.
N. Mujahid et al. A UV-independent topical small-molecule approach for melanin production in human skin. Cell Reports. Vol. 19, June 13, 2017, p. 1. doi: 10.1016/j.celrep.2017.05.042.
J.A. D’Orazio et al. Topical drug rescue strategy and skin protection based on the role of Mc1r in UV-induced tanning. Nature. Vol. 443, September 21, 2006, p. 340. doi: 10.1038/nature05098.
N. Seppa. UV Blocker: Lotion yields protective tan in fair-skinned mice. Science News. Vol. 170, September 23, 2006, p. 196.