Cancer Cells Killed With Nutrient Deprivation

While all cells depend on nutrients to grow, cancer cells are more ravenous than others as they need to alter their metabolism in order to provide additional fuel to survive, grow and spread.

New findings published in the journal Cancer Research examine how nutrient deprivation can kill kidney cancer cells.

Researchers at Duke University deprived the cancerous cells of amino acid cysteine during the study; this helped trigger the form of cell death known as necrosis in mouse models carrying the disease.

"We found that the same machinery that makes these tumors so aggressive also makes them vulnerable to nutrient deprivation," said senior study author Jen-Tsan Ashley Chi, Ph.D., associate professor of molecular biology and microbiology at Duke University School of Medicine, in a news release. "It is like we are beating it at its own game."

As about three-fourths of renal cell carcinomas are marked by a missing VHL tumor-suppressor gene that prevents the development of tumors in healthy cells, researchers decided to investigate how single genetic change could alter the metabolism and nutrient requirement of cancer cells.

During a nutrient deprivation test, researchers removed each o the 15 amino acids from their growth media. While many of the cells weathered the change fine, when cysteine was removed, the cells swelled up and floated to the surface-a sign of neurotic death.

Then, the researchers conducted numerous genetic analyses to determine the network of genes responsible for nutrient addiction. Normally the VHL gene acts to suppress another gene known as tumor necrosis factor alpha or TNF-alpha. However, when VHL is lost, high levels of TNF-alpha give rise to a more aggressive form of cancer that sheds dangerous free radicals. 

Cystine works by maintaining high levels of antixoidants that disarm free radicals of oxygen. Therefore, when researchers got rid of the nutrient, the cancer cells essentially diet by their own hand of free radical damage, researchers say. 

The researchers showed that the approach was successful both in tissue culture cells as well as in mice. Tang and his colleagues in the laboratory of Dr. David Hsu at the Duke Cancer Institute implanted renal cell carcinoma tumors into mice and then treated the animals with sulfasalazine, a drug that blocks cystine uptake. They found that the treatment induced necrosis and significantly delayed tumor growth.

With future research and by targeting cancers for destruction by necrosis and not by apoptosis, the study authors believe there is a great promise for therapeutic treatments.

"Most chemotherapies kill cancer cells through apoptosis, and the cancer cells that escape apoptosis are the root cause of chemotherapy resistance and tumor progression," said Chi. "Cystine starvation treatments could address resistance by killing cells through a different mechanism."

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