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CCMTR Research Discovers Compound That May Inhibit Tumor Growth

 

By Jason deBruyn

Triangle Business Journal

While studying the origins of intestinal birth defects, researchers at North Carolina State University believe they might have found a way to stop the growth and spread of cancerous tumors.

Nanette Nascone-Yoder, an assistant professor of molecular biomedical sciences, typically researches birth defects, particularly in the gastrointestinal tract. During a screening of chemical compounds of one such study that used frog embryos, she and associate chemistry professor Alex Deiters discovered a compound that induced heterotaxia, a disordering or mirror-image "flipping" of internal organs, according to a report published in the Feb. 24 issue of Chemistry & Biology.

The researchers dubbed the compound "heterotaxin" and found that it has other effects, particularly as it might relate to tumors in humans. They determined that the pathway most likely to be affected by heterotaxin was the TGF-beta pathway, which is known to play a role in the progression of cancerous tumors.

"This was exciting because tumors have to have cells that can migrate and form a blood supply in order for the canĀ­cer to spread," Nascone-Yoder said. "Heterotaxin inhibits those processes, which may make it a good 'lead' candidate for the development of an anti-tumor drug."

The researchers made clear that they are only in the beginning stages of determining the compound's efficacy and have tested it only in petri dishes. They do not know what specific effect it could have on humans at this point.

"Could they have a big impact? It's possible," N.C State associate professor of oncology Marlene Hauck says. On the other hand, there could be downside to the way the compound is currently structured. For example, it could be too toxic to benefit humans, Hauck notes. "They may be able to devise a drug that has the impact we want without the toxicity," she says.

"I want to emphasize that this is in the very early stages," Nascone- Yoder said.

Still, at least in a petri dish, experiments with Hauck and cell biologist Philip Sannes showed that heterotaxin quenches the growth of canine tumor cells, and inhibits some of the changes required for human tumor cells to become migratory and invasive, according to the published report.

Deiters developed new chemistry in his N.C. State lab to synthesize the chemical structures used in the biological experiments. He says the compound itself or a derivative of it could become a new drug, or it could be used as a tool, in conjunction with other components, to discover new anticancer drugs.

On a more personal level, the researchers say they enjoyed working together partly because their fields of research are typically separate.

"Our worlds don't overlap that much," Hauck said. "This was a fun project, honestly."

For Nascone-Yoder, the collaboration helped lead to the new discovery.

"The little, tiny eureka moments always lead to more questions," she says. "You call up your colleagues, and do experiments, then you finally get it together."

Posted March 18, 2012

Drs. Nascone-Yoder, Sannes, and Hauck are members of the College of Veterinary Medicine. Dr. Deiters is a member of the College of Physical and Mathematical Sciences. The research team is part of the NC State Center for Comparison Medicine and Translational Research. The CCMTR is a community of more than 100 scientists from five NC State colleges. These investigators are involved in collaborative ”One Health” studies with government, private, and other academic researchers to advance knowledge and practical applications that improve the health of animals and humans.