Editors' ChoiceCancer

Self-tanning cells, the new SPF

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Science Translational Medicine  05 Jul 2017:
Vol. 9, Issue 397, eaan8202
DOI: 10.1126/scitranslmed.aan8202


A skin-penetrant small molecule activates melanin production to protect cells from cancer-inducing ultraviolet damage.

A day at the shore can mean sand, surf, and the obligatory reapplication of sunscreen at regular intervals. The latter, although perhaps not the highlight of a beach trip, is essential to protect our skin from damaging ultraviolet (UV) rays that can directly contribute to the development of skin cancer. Current sunscreen works by absorbing or reflecting UV light, but what if there was a way our cells could directly fight back against the sun’s rays? In a recent report, Mujahid et al. demonstrate how this could be done by generating a topical small molecule that stimulates skin cells to generate UV-protecting skin pigmentation.

The authors focused on targeting salt-inducible kinase 2 (SIK2), a protein that can block pigment production by negatively regulating a key driver of melanin expression, microphthalmia-associated transcription factor (MITF). They first used a previously reported SIK inhibitor to demonstrate they could modulate melanin production in human melanocyte cell culture models. This same inhibitor was also able to stimulate the pigmentation pathway via topical application in a mouse model mimicking fair-skinned humans, who are more prone to sun-induced skin damage. Although the inhibitor was effective at increasing melanin in rodent models, it could not efficiently penetrate human skin. To overcome this limitation, the authors set out to generate second-generation SIK inhibitors that could readily be absorbed by the human epidermis. The new inhibitors were tested in human skin explants, with successful penetration of the skin barrier and increased melanin production. The authors also tested the duration of protection of this new approach and determined that the increase in pigmentation was transient in nature, with gradual reversal back to pretreatment state by two weeks after the final application of the inhibitors.

Future studies will be needed to fully confirm the utility and safety of this approach to UV protection. Nonetheless, the concept of someday achieving a sunscreen reapplication–free day at the beach does carry appeal.

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