Alumnus’s discovery may lead to new weapons against skin cancer

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Joshua Williams completed his PhD degree in pharmaceutical sciences in 2010 and along the way discovered a phenomenon that may lead to a weapon in the fight against skin cancer.

The research, which was published in the Journal of Photochemistry and Photobiology B, Biology and Drug Week,showed that optimizing levels of the nutrient folate in human skin can help prevent and repair the carcinogenic effects of exposure to sunlight.

Williams did the research under the guidance of Myron Jacobson, PhD, College of Pharmacy research professor, at Jacobson’s lab at the Arizona Cancer Center.

Folate (or folic acid, the synthetic derivative of folate) is an essential nutrient for human beings. Folate nutrition is important to support dividing cells as they are replicating DNA. A high dietary folate intake is associated with a diminished risk of many types of cancer. Williams’ research set out to study the effects of folate and sunlight on the skin.

“Skin is dividing tissue,” says Williams. “It is constantly replacing itself, so its nutrient demands are higher than other tissue in your body. However, skin is last in line for delivery of nutrients. In addition, exposure to sunlight contributes to decreased folate nutrient levels specifically in skin tissue.”

The Study

To study the effects of folate on skin, Williams examined a culture of human skin cells, which allowed control of his experiment. As far as Williams is aware, no other researchers had done this type of work on skin cells before.

Next, Williams studied the consequences of inadequate folate nutrition by removing folate from skin cells. His research confirmed that if you take folate away, skin cells stop dividing at a very specific point in the division process: the point at which they are replicating DNA. This phenomenon had not been confirmed in skin cells before. Folate restriction, Williams observed, also resulted in increased levels of DNA damage.

Williams then exposed the folate-depleted skin cells to UV radiation similar to sunlight and measured the results. He found that the cells were less able than cells that have sufficient folate nutrition to repair damage, such as DNA breaks, that resulted from sunlight exposure and folate restriction.

Even more startling was the fact that when Williams re-introduced folate to the depleted skin cells, the negative effects of folate restriction were completely reversed. The cells quickly began to repair the DNA damage induced by folate deficiency and resumed normal cellular division.

“Thus,” wrote Williams and Jacobson in their research report, “folate deficiency creates a permissive environment for genomic instability, an early event in the process of skin carcinogenesis. Optimizing folate levels in skin is beneficial in preventing or repairing the pro-carcinogenic effects of UVR exposure.”

“In my view, this is very newsworthy,” says Jacobson, Williams’ adviser. “The published paper cited in Drug Week is the first definitive evidence that optimal folate status is crucial for the health of skin, specifically as it relates to sun damage to skin. Consequently, this has potentially very interesting implications for skin cancer, which has an incidence higher than all other cancers combined.”

The Future of Folate Research

Williams, who now works for the BIO5 Institute on the UA campus, is excited about the future of research into the effects of folate on skin. He has many questions that are still unanswered.

“You might think that if some folate is good, a lot must be better,” he says. “It’s not necessarily so. We need to continue to develop sensitive and accurate methods to measure folate in human biological systems.”

Another question he is looking to answer is what kind of folate treatment would be the most beneficial for people who take it.

“I’d also like to investigate the question, ‘Is oral folic acid sufficient to restore folate to skin – or do you need an additional topical application, as in a cream?’” he said. “I also want to quantify sunlight’s ability to degrade folate.”

While there is still much to learn about the role of folate in the prevention and treatment of skin cancer, what Williams has already discovered is a breakthrough.

“Josh’s work is pioneering,” says David Alberts, MD, director of the Arizona Cancer Center. “The discoveries he has made will give researchers important new tools in the war against skin cancer.”

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