September 14, 2011

X-ray protein probe leads to potential anti-cancer tactic

Research into a type of protein, important for the runaway growth of cancer cells, surprisingly led to a new type of potential anti-cancer drug.

Emory researchers Haian Fu, Jing Zhao and Yuhong Du were using X-rays to see how a compound called FOBISIN fits into the structure of 14-3-3 proteins. Unexpectedly, the X-rays induced the compound to be permanently bonded to the protein. The finding suggests that compounds like FOBISIN can be used in combination with radiation to trigger potent anticancer activity.

The results were published online Sept. 9 in Proceedings of the National Academy of Sciences Early Edition.

Senior author Fu, who has been studying 14-3-3 proteins for two decades, is professor of pharmacology and of hematology and oncology in the School of Medicine, and director of the Emory Chemical Biology Discovery Center. Zhao is a postdoctoral fellow and Du is assistant professor and associate director of the discovery center.

The finding suggests that compounds like FOBISIN could be developed as "pro-drugs" that upon exposure to radiation, permanently stick to and inhibit their targets. A common strategy in fighting cancer is to combine drugs and radiation so that the drugs increase cells’ sensitivity to radiation. Here, the radiation would activate the drug.

"These compounds could be used in combination with other strategies to enhance the tumor selectivity of the treatment," Fu says.

The research was funded by the U.S. National Institutes of Health, the Georgia Cancer Coalition, and the Georgia Research Alliance.

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