Cancer cells have been long known to have a “sweet tooth,” using vast amounts of glucose for energy and building blocks for cell replication.
Now, a study by a team of researchers at Johns Hopkins and elsewhere shows that lymph gland cancer cells called B cells can use glutamine amino acids in the absence of glucose for cell replication and survival, particularly under low-oxygen conditions, which are common in tumours.
In the 4 January edition of Cell Metabolism journal, Dr. Anne Le and a team of investigators collaborating with the Johns Hopkins Brain Science Institute, said the finding is critical for developing innovative cancer therapies because it offers “proof of concept” evidence that curbing the growth of B cell cancers can be accomplished by inhibiting a glutamine enzyme called glutaminase.
Dr. Le noted that although little is known about glutamine’s role in the growth of B cell cancer, the amino acid circulates in the blood at the highest level among the 20 amino acids that do so.
The tricarboxylic acid cycle (TCA or Krebs cycle) is classically regarded as a pathway for glucose oxidation. However, the experiments by Dr. Le and the team show that B cells oxidise glutamine when glucose is absent.
The study also found that when oxygen is scarce, there is enhanced conversion of glutamine to glutathione, an important agent for controlling the accumulation of oxygen-containing chemically reactive molecules that cause damage to normal cells.
When the investigators used a glutaminase inhibitor, cancerous growth of B cells was stopped in petri dishes.
“The flexibility of the TCA cycle in using both glutamine and glucose pathways may be important for cancer cells to proliferate and survive, especially under the low-oxygen and nutrient-deprived conditions often encountered in the tumour micro-environment,” said Dr. Le.
Now, perhaps, scientists can exploit that survival strategy to stop cancer, according to former Johns Hopkins scientist Dr. Chi Dang, now at the Abramson Cancer Center at the University of Pennsylvania. “A broader and deeper understanding of cancer cell metabolism and cancer cells’ ability to reprogramme biochemical pathways under metabolic stress can be a rich ground for therapeutic approaches targeting tumour metabolism,” he said.
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