A Topical Solution to the Sunless Tanning Problem

Abstract

Skin cancer is the most commonly diagnosed type of cancer and is strongly associated with UV exposure and skin pigmentation. Recent advances in pharmacologic non-UV tanning methods open the possibility of preventing melanoma and non-melanoma skin cancer, especially in people who do not tan in the sun.

Figure 1. Mechanisms of UV-Dependent and -Independent Tanning

Ultraviolet (UV)-associated DNA damage in keratinocytes leads to cleavage of pre-opiomelanocortin (POMC) and production of alpha-melanocyte stimulating hormone (α-MSH), which binds to the melanocortin 1 receptor (MC1R) in melanocytes. MC1R binding results in increased cAMP, activation of protein kinase A (PKA), and phosphorylation of the c-AMP responsive element binding protein (CREB). CREB phosphorylation leads to increased transcription of MITF, which initiates the melanin production cascade resulting in increased melanin. Melanin is packaged in melanosomes and then transferred to keratinocytes to protect their nuclei against further UV damage. SIK inhibits MITF transcription in the absence of UV-damage, preventing melanin production. Pharmacological inhibition of SIK with HG 9-91-01, YKL 06-061, or YKL-060062 leads to UV-independent tanning [2].