Could a small molecule prevent melanoma in redheads?

If you are a redhead, you have likely spent most of the summer attempting to escape those skin cancer-causing rays that seem to victimize you more than others. But a new study may allow redheads to enjoy the sunshine a little more, after finding a potential strategy to reduce their risk of melanoma.

Study co-author Rutao Cui, Ph.D., a professor of pharmacology and experimental therapeutics and a professor of dermatology at Boston University School of Medicine in Massachusetts, and colleagues recently reported their findings in the journal Nature.

Melanoma is a form of skin cancer that begins in melanocytes. These are cells that produce a pigment called melanin, which helps to protect the deeper skin layers against the harmful effects of ultraviolet (UV) radiation from the sun.

According to the American Cancer Society (ACS), melanoma only accounts for around 1 percent of skin cancers in the United States, but it does account for a large number of skin cancer deaths.

It is a well-established fact that people with red hair, fair skin, and freckles are at increased risk of melanoma. Previous research has shown that this may be because redheads are more likely to possess variants in a protein called melanocortin-1 receptor (MC1R), which may reduce skin pigmentation.

However, Dr. Cui notes that the precise mechanisms by which these MC1R variants might increase melanoma risk in redheads have been unclear.

"Up until now," he explains, "our understanding of the molecular biology of melanomagenesis (developing melanoma cancer) lacks explanations for how MC1R is affected by UV radiation, why redheads are more prone to melanoma, and whether the activity of red hair color variants could be restored for therapeutic benefit."

To help answer these questions, Dr. Cui and team conducted a series of experiments on cultured skin cells and mouse models.

Melanoma and M1CR palmitoylation

First, the researchers exposed cultured skin cells that carried MC1R variants to UV radiation.

In response to UV radiation, the researchers identified a reduction in palmitoylation in the M1CR protein of skin cells.

Palmitoylation is a process that is crucial for prompting MC1R signaling and pigmentation. Lack of palmitoylation can reduce skin pigmentation and increase skin cancer risk.

Next, the team sought to determine whether or not increasing palmitoylation in the M1CR protein might help to protect against skin cancer.

They assessed two groups of mice possessing MC1R variants. One group was treated with a small molecule called palmostatin B, which is known to trigger palmitoylation, while the other group remained untreated.

On exposing both groups to UV radiation, the researchers found that the mice treated with palmostatin B were less likely to develop melanoma, compared with the untreated rodents.

According to Dr. Cui and colleagues, the study results indicate that increasing M1CR palmitoylation in skin cells might be a feasible way to reduce the risk of melanoma in redheads.

"We hope our study allows for the development of a pharmacological prevention strategy for redheaded people to protect their skin and let them enjoy the sun like other people."

Rutao Cui, Ph.D.