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A common antidepressant drug may also inhibit the growth of cancer cells, suggests a new study published in Molecular Cancer Therapeutics.
Sertraline is one of the most prescribed drugs in the United States and is used to combat depression, but when studied on cell cultures and animal models, it was also found to directly inhibit cancer growth while leaving normal cells unharmed. As the drug is already established to be safe for regular use, repurposing it for fighting cancer is a promising treatment option.
The discovery was made after scientists identified a possible mechanism to target cancer cells. Malignant cancer cells grow much faster than normal cells until they become a dangerous tumor. Whilst they grow, they require large amounts of amino acids and other precursors to sustain their growth. These amino acids are synthesized within the cell to create essential proteins, but some cancer cells synthesize them at a much higher rate than normal cells.
In fact, some cancer cells rely on two specific amino acids, serine and glycine, to such an extent that they become ‘addicted’, and scientists believe if they can stop the production of these amino acids, they can halt the growth of cancer cells.
"This mechanism is an interesting target because cancer cells are so dependent on it," said Professor Kim De Keersmaecker, head of the Laboratory for Disease Mechanisms in Cancer (LDMC), in a statement. "Healthy cells use this mechanism to a lesser extent and also take up serine and glycine from food. This is not sufficient for cancer cells, however, meaning they start producing more. If we can halt this production, we will be able to fight the cancer without affecting healthy cells."
Serine/glycine addiction is still a poorly understood mechanism, but the authors believe that further understanding may spur novel drug treatments for fighting some cancer growths. Many common types of brain, lung, and skin cancer, as well as T-cell leukemia, overproduce serine and glycine.
In an attempt to target this mechanism and prevent cancer growth, the scientists used a large database of existing drugs to test for candidates. After testing 1,600 drugs on yeast cells, the antidepressant sertraline was found to be the most effective at preventing the synthesis of serine and glycine. Previous studies have suggested sertraline has anti-cancer properties in mouse models, but the underlying mechanisms remained elusive.
When they tested sertraline on mouse models with breast cancer, they found the drug worked well in combination with antimalarial drugs to reduce cancer growth. Sertraline, therefore, may slow selective serine/glycine dependant cancers, particularly if used as part of a multi-treatment approach with mitochondria metabolism inhibitors.
For now, studies on sertraline have only been demonstrated in mouse xenografts, so it remains to be seen if it will translate to humans. In addition, many cancers have unique growth mechanisms and further study is needed to understand whether sertraline is a viable treatment option for multiple cancers. However, the authors remain hopeful that further research will clarify sertraline’s potential.
"These are, of course, results of experimental research, not clinical studies, but we can be optimistic about the potential. The safety of using sertraline in humans has already been well described, which is a great advantage. That's why we are also looking for industrial partners to develop this further," said Professor De Keersmaecker.
