The Use of Analogs of α‐MSH as Tanning Agents for the Prevention of Melanoma

Abstract

Listen

Translate article

Melanoma, the deadliest form of skin cancer that originates from melanocytes, continues to increase at an annual rate of 4%. Exposure to solar ultraviolet radiation (UV) is causal for melanoma, especially in those with fair skin and poor tanning ability. α‐Melanocyte stimulating hormone (α‐MSH) plays a key role in regulating pigmentation by binding and activating the melanocortin 1 receptor (MC1R) that is expressed on the cell surface of melanocytes. Additionally, activation of the MC1R increases the DNA repair capacity of melanocytes, thereby reducing the DNA damaging effects of UV and mutations, the underlying cause of melanoma. Certain allelic variants of the MC1R gene are associated with red hair, fair skin, and poor tanning ability. This phenotype increases sensitivity to UV and the risk of melanoma. About 30% of the white population in America is heterozygous for one MC1R variant, which increases melanoma risk. The laboratory is developing a melanoma prevention strategy based on utilizing small peptide analogs of α‐MSH that activate the MC1R. Analogs of α‐MSH will be tested for their ability to protect from the deleterious effects of UV by reducing DNA damage, inflammation and sunburn, and apoptosis, and increasing pigmentation in melanocytes contained in cultured human skin substitutes. The tetrapeptides LK 184 at 10 nM, LK 467 at 100 nM, and the tripeptide LK 514 at 1 μM, were tested for their ability to stimulate pigmentation of engineered human skin substitutes (ESS) containing melanocytes. To determine the effects of LK 467, LK 184, and LK 514 on pigmentation, the ESS were treated for 3, 10 or 15 days daily with either peptide. The effects of the three analogs were quantified using Fontana Masson stain to assess their ability to stimulate pigmentation by synthesizing melanin. The analogs showed promising effects in their ability to induce synthesis of melanin, which induces pigmentation. These experiments helped in the progression of determining the efficacy of these analogs in photoprotection and advance their testing in a clinical trial.