We are a nation of anxious people. Ten percent of Americans take antidepressants, and more than 60 percent of those people have taken them for 2 years or longer. Usually stats like these are a cause for hand-wringing, but new information about how antidepressants may work against prostate cancer may be putting a new spin on everything.
Scientists have discovered an enzyme that assists prostate cancer in spreading into bones. They have also learned that many antidepressants contain agents that block the production of that enzyme.
It is usually the bones which see the first spread of metastasizing prostate cancer. Accordingly, approximately 90 percent of all prostate cancer deaths involve bone metastasis.
The new study describes how the enzyme MAOA triggers a signaling cascade that simplifies the process by which prostate cancer cells spread to the bone. It stimulates three proteins to amplify the function of osteoclasts. These are bone cells that play a role in the degradation of bone tissue during growth and healing.
"The cancer cells can specifically activate the osteoclasts for bone degradation," said Study co-author Jason Wu. "The experimental phenomenon we've observed is actually a lot more bone destruction than new bone formation."
Lower the incidence of MAOA, the researchers found, and you reduce the cells' ability to spread to the bone. Conversely: “If we overexpress this enzyme in prostate cancer cells, we found increased bone metastasis in mice," said Wu.
When the scientists introduced a drug known as clorgyline – an antidepressant known to block MAOA – into the prostate cancer lines, they noted how the drug prevented MAOA from activating the three proteins that enhance osteoclast function. Accordingly, the ability of prostate cells' ability to metastasize and grow into the skeletal structure was diminished.
"Our findings provide a rationale to pursue the new use of these 'old' antidepressant drugs to benefit late-stage prostate cancer patients with signs and symptoms of metastasis,” said Wu.
Clorgyline is not the only antidepressant in clinical use that works the way it does. Among the research team's next steps is working through that list of drugs and seeing what effect they have on cancer metastasis.
"Our studies provide promising results in mice, which merit further investigation, such as adjusting the formulation, dose, and delivery route of MAOA inhibitors, prior to ultimate clinical application," notes Wu.
The study was published in the journal Cancer Cell.