Protecting Human Melanocytes from UV-Induced DNA Damage

Zalfa A. Abdel-Malek, Ph.D.
University of Cincinnati College of Medicine
R01ES09110

Researchers at the University of Cincinnati developed three peptides that mimic a naturally occurring hormone that results in tanning and enhances the DNA repair capacity in pigment producing cells known as melanocytes. The natural hormone is alpha melanocyte stimulating hormone (α-MSH), which is a peptide hormone made up of 13 amino acids that is released from the pituitary gland and stimulates melanocytes to produces the pigment melanin which causes tanning after exposure to the sun. The synthetic peptides, or analogs, are each four amino acids in length and share a common sequence with the natural hormone. Two of the analogs were found to be more potent than α-MSH in stimulating production of melanin, reducing apoptosis and release of hydrogen peroxide, and repairing UV-induced DNA damage in cultured human melanocytes.

Melanoma results when melanocytes in the skin develop DNA damage that overwhelms their inherent DNA repair capacity. Melanoma is the deadliest form of skin cancer. Since there is no known cure, limiting sun exposure and the use of sunscreens, has become the primary focus of preventing the disease. Melanoma incidence is increasing, especially in parts of the world where sun exposure is high. For instance in Australia, 1 in 35 women and 1 in 25 men will have at least one melanoma during their lifetime.

The authors believe that these analogs could be developed into topically applied creams that would protect the skin from UV-induced cancers. This could be especially important for individuals at high risk of melanoma such as those with a family history of the disease or life-styles or occupations that cause extended sun exposure.

Citation: Abdel-Malek ZA, Kadekaro AL, Kavanagh RJ, Todorovic A, Koikov LN, McNulty JC, Jackson PJ, Millhauser GL, Schwemberger S, Babcock G, Haskell-Luevano C, Knittel JJ. Melanoma prevention strategy based on using tetrapeptide alpha-MSH analogs that protect human melanocytes from UV-induced DNA damage and cytotoxicity. FASEB J. 2006 Jul;20(9):1561-3.