Molecule 968 binds glutaminase and starves cancer cells

The key to this research is the amino acid glutamine. Researchers have long believed that starving cancer cells of glutamine, which cancer cells require in larger quantities than normal cells, would help fight some cancers. Now, they have discovered a molecule that does the job: Dubbed 968 by investigators, this proof of concept molecule binds to the enzyme glutaminase to inhibit cancer growth by blocking the cancer cells' utilization of glutamine.

Cancer cells demand a tremendous amount of energy, says Richard Cerione, the Goldwin Smith Professor of Pharmacology and Chemical biology. The finding could lead to a new class of drugs, capable of halting cancer progression without harming normal cell growth, he said.

After discovering that 968 inhibited glutaminase and effectively shrunk tumor cells, Cerione and his research team tested the molecule to understand its effects on non-cancerous cells.

"We have effectively stopped the growth of breast cancer cells in the lab without affecting normal mammary cells," said Cerione, who is now investigating the impact of 968 on other forms of cancer, including prostate, ovarian and pancreatic cell lines. "We've validated our target. The next step will be to further the development of a classes of small molecules capable of stopping cancer cell growth in humans." To that end, Cerione and colleagues are currently working with the KensaGroup, of Ithaca, N.Y., in addition to Cerione's academic pursuits exploring the effects of 968 and glutaminase on cancer cell growth.

"Our research has highlighted a previously unrecognized connection between the cell's metabolic machinery and the signaling pathways and growth factor receptors that regulate cell growth," said Cerione. He believes there is a broader connection between metabolism and cell signaling for other areas in biology and biomedicine.

Cornell co-authors of the research include postdoctoral associate Jianbin Wang (co-first author), and senior research associates Jon Erickson (co-first author), Kristin Wilson and Sekar Ramachandran. Funding for the research: The National Institutes of Health and the Susan G. Komen Foundation.