Novel compounds activate pigmentation pathway without damaging UV radiation
Investigators at Massachusetts General Hospital (MGH) and Dana-Farber Cancer Institute (DFCI) have developed a way of increasing pigmentation in human skin without the damaging effects of ultraviolet (UV) radiation. Their study, reported in the June 13 issue of Cell Reports, is a follow-up to a 2006 study that identified the molecular pathways underlying the tanning response and induced tanning in a strain of mouse that normally does not produce the protective, dark form of melanin.
“The activation of the tanning/pigmentation pathway by this new class of small molecules is physiologically identical to UV-induced pigmentation without the DNA-damaging effects of UV,” says David E. Fisher, MD, PhD, chief of the Department of Dermatology at MGH who led both studies. “We need to conduct safety studies, which are always essential with potential new treatment compounds, and better understand the actions of these agents. But it’s possible they may lead to new ways of protecting against UV-induced skin damage and cancer formation.”
In the 2006 study published in Nature, Fisher’s team – then based at DFCI – used a topical compound called forskolin to induce tanning in a strain of red-haired mice, in which a genetic variant interrupts the pathway leading to production of melanin pigment. Forskolin activates a protein further down the pigmentation pathway, bypassing the interruption and inducing production of the protective dark pigment called eumelanin.
Subsequent testing in human skin samples of forskolin and a related compound with similar action was not successful, probably because human skin is around five times thicker than the skin of mice. This led the investigators to explore a different approach. Enzymes called salt-inducible kinases (SIKs) were known to regulate transcription of a protein even further down the pigmentation pathway, and inhibiting SIK expression had been shown by a research group in Japan to activate pigmentation in mice.
