UA researchers discover compound that could target malignant melanoma cells

Source: KVOA.com, March 2015

TUCSON – Researchers with the University of Arizona College of Pharmacy and the Arizona Cancer Center have found a novel compound that could be used to target malignant melanoma cells, which are cells that believed to be the cause of many skin cancer-related deaths.

Associate professor in the UA College of Pharmacy Department of Pharmacology and Toxicology, George Wondrak and doctoral student at the College of Pharmacy, Angela Davis hope that they can help aid the treatment of skin cancer, the most common form of cancer.

They published their discoveries in the Journal of Biological Chemistry.

According to the American Cancer Society, Melanoma is a malignant tumor derived from pigment-producing cells that causes most deaths attributed to skin cancer.

The researchers were able to screen for compounds that destroy melanoma cells after determining its relationship and response to stress. They found that an organic compound used in manufacturing dyes assembled in the Wondrak laboratory known as aurin may be the key in destroying the melanoma cells by undermining the cell’s resilience and resistance to stress according to the UA College of Pharmacy.

“We were excited to see that aurin, the most promising compound identified in our experiments, was able to eliminate melanoma cells without causing harm to normal cells,” said Davis.

The researchers discovered through a detailed gene expression analysis that aurin activates the melanoma cells’ heat shock response.

“After it became clear that aurin acted as a potent heat shock response inducer, we then explored how our lead compound was able to achieve these striking effects,” said Dr. Wondrak.

They soon discovered in follow-up studies that aurin was an inhibitor of a major defense system in melanoma cells. This defense system aids the cells to quickly adapt and become resistant to therapies. They also discovered that aurin inactivates a protein known as Hsp90 which enables the cells to adapt to stress and chemotherapy.

“Once we knew that aurin inactivates Hsp90, it all made sense,” said Davis. “The finding that aurin blocks the function of this defense protein is significant. Hsp90 inhibitors are now under consideration as novel treatments that make cancer cells more sensitive to other therapeutics by undermining their ability to deal with stress.” The team hopes for future follow-up experiments on aurin.

To view the published results, view the most recent issue of the Journal of Biological Chemistry.