Serotonin is often described as the “happy chemical” due to its well-known role in regulating mood. But how does it affect oncology?
However, recent research suggests that this familiar molecule may have an unexpected role in the development of cancer — not through its effects on the brain, but through a completely different mechanism in other parts of the body.
Although serotonin is normally associated with the brain, about 95% of the body’s serotonin is produced in the intestine. From there, enters the bloodstream and travels to various organs and tissues, including the liver, pancreas, muscles, bones, adipose tissue and cells of the immune system.
Intestinal serotonin helps regulate blood sugar levels through its actions on the liver and pancreas, and regulates body temperature by acting on adipose tissue. It also contributes to maintain healthy bonesstimulates appetite and intestinal motility, promotes sexual health, wound healing and supports immunity against harmful microorganisms. Essentially, serotonin controls the functions of many cells in the body, and its effects go far beyond mood regulation.
Serotonin and cancer genes
In 2019, scientists at the Icahn School of Medicine at Mount Sinai (New York) discovered that serotonin can enter cells and interact directly with DNA. They found that it binds to molecular “switches” that control whether genes are active or inactive — and this binding can activate specific genes.
Since then, studies have shown that serotonin can activate genes involved in cancer growth. This mechanism was observed in brain, liver and pancreas cancers — and may be present in many other types of cancer.
At the University of Limerick (Ireland), a team is investigating the interaction between serotonin and DNA to better understand how it influences cancer. Identifying the exact sites where serotonin binds to cancer-related genes could support the development of targeted epigenetic therapies – treatments that control which genes are turned on or off.
What are epigenetic therapies?
Epigenetic therapies aim to reprogram cancer cells by directly adjusting their genetic activity. They can turn off harmful genes and turn on beneficial genes without changing the DNA sequence.
These therapies could one day attack cancer cells with greater precision than current methods — surgery, chemotherapy and radiotherapy — which, although they can save lives, are aggressive, have significant side effects and do not always prevent recurrences.
How does intestinal serotonin reach cancer cells?
Scientists are also exploring how serotonin produced in the intestine reaches cancer cells. Understanding this pathway could allow doctors to control serotonin levels in patients. Possible approaches include dietary changes, maintaining a healthy gut microbiome, or using antidepressants known as selective serotonin reuptake inhibitors (SSRI).
Cells take up serotonin through small “transport channels,” and SSRIs block these channels, limiting the entry of serotonin into cancer cells. These medications increase serotonin levels in the body, but prevent it from reaching DNA and exerting potential cancer-promoting effects. This strategy can complement existing therapies and possibly increase their effectiveness.
Uncovering the double life of serotonin
Serotonin in the brain and in the gut function largely independently. Serotonin, which influences mood, does not appear to contribute to cancer growth. For example, people with depression may have lower serotonin activity in the brain, but serotonin produced in the gut does not appear to directly affect brain serotonin.
SSRI antidepressants — such as Prozac, Celexa, and Zoloft — work by increasing serotonin levels in the brain. Therefore, anyone taking these medicines need not fear that they may promote cancer.
On the contrary, preliminary studies suggest that SSRIs may have beneficial effects against certain types of cancer, although larger clinical trials are needed to confirm this hypothesis.
The future of research
Our goal is to build a detailed understanding of the role of serotonin in different tissues and cellular pathways, potentially opening new therapeutic avenues. However, major challenges remain.
It is necessary to better understand how serotonin interacts with cancer-related genes to identify the most effective targets. It is also essential develop accurate delivery systems that ensure that epigenetic medicines reach the right location.
And, above all, the encouraging results obtained in cell experiments need to be validated in animal studies and ethically conducted human clinical trials.
If we can develop therapies that specifically target serotonin activity in cancer cellstumors may become less aggressive and easier to remove surgically, with a lower risk of recurrence.
A more complete understanding of serotonin’s functions in the body — in mood, metabolism and cancer — could guide the development of more precise and effective therapies in the future.
