Serotonin Makes Tumors Happy Too

Serotonin or 5-hydroxytryptamine (5-HT) is a neurotransmitter primarily found in the gastrointestinal tract (GI tract), blood platelets, and the central nervous system of humans. Serotonin is manufactured in the brain and the intestines and is primarily stored in and transported by platelets. It is popularly thought to be a contributor to feelings of well-being and happiness. It mediates gut movements (diarrhea) and the temperature in the body (fever).

Next to its well-known functions, serotonin has been shown to be a mitogenic factor for a wide range of normal and tumoral cells. Serotonin exhibits a growth stimulatory effect in aggressive cancers and carcinoids usualy through 5- HT1 and 5-HT2 receptors. Serum serotonin level was found to be suitable for prognosis evaluation of urothelial carcinoma in the urinary bladder, adenocarcinoma of the prostate and renal cell carcinoma.

In line with the above, during tumor progression, tyrosine hydroxylase, the rate-limiting enzyme in the serotonin biosynthesis pathway, is often up-regulated.

Following experimental results, it has been suggested that serotonin promotes tumor growth and survival in

Liver Cancer

Pancreatic Cancer

Breast Cancer

Blader Cancer

Colon Cancer

And Others

It was previously indicated that the 5-HT-1 and 2 receptors are extensively expressed in the human breast cancer, prostate cancer, bladder cancer cells and other cancer types. Therefore the inhibition of these receptors has been proposed to be a good strategy to stop tumor growth.

Qunine and Chloroquine: Interestingly, it has been recently reported in the Nature magazine that the antimalaria drug Quinine that is also known to have anti cancer actions (its derivative chloroquine has strong anti cancer effects as well) interferes with serotonin biosynthesis and action. I just checked some older studies and it appears that chloroquine is a competitive inhibitor of serotonin uptake by platelets.

Sorafenib: it has been well-known that sorafenib produces anticancer effects through targeting multiple kinases, but it was shown recently that it has “off-target” 5-HTR binding activity.

Cyproheptadine: sold under the brand name Periactin or Peritol, is a first-generation antihistamine with additional anticholinergic, antiserotonergic, and local anesthetic properties. It is a 5-HT2A receptor antagonists. Cyproheptadine can also be used as an appetite stimulant in cancer patients in order to improve their appetite and may be helpful in patients with cancer anorexia/cachexia. It is not know if the anticancer mechanisms of this drug are related to its antiserotonergic or antihistamine action but its potential is clear.

Propranolol: I was unaware about the fact that Propranolol which is known to have major anti cancer effects. it is also an inhibitor of 5-HT1B. Others have suggested that propranolol acts as a 5HT1A antagonist and a 5HT1B agonist in the rat cortex. Maybe its modulation of the serotonin receptors is the origin of its known anti angiogenesis effect ....

cancertreatmentsresearch.co...

[Heilung18-Gesund]

Obvious caveats: tissues - pancreatic and colorectal; animal models; no human trials or RCTs.

Sci Transl Med. 2021 Sep 15;13(611):eabc8188. Attenuation of peripheral serotonin inhibits tumor growth and enhances immune checkpoint blockade therapy in murine tumor models

The neurotransmitter serotonin is known to be involved in cell proliferation and cancer,

syngeneic mouse models of pancreatic and colorectal cancer.

genetic knockdown of peripheral serotonin enhanced CD8+ T cell accumulation in tumors and reduced tumor growth.

fluoxetine and telotristat enhance the effects of anti–PD-1 therapy to induce long-term tumor control in mice. improve cancer immunotherapy that warrants further clinical investigation.

News text précis:

Classic antidepressants slowed the growth of pancreatic and colon cancers in mice.

When combined with immunotherapy, they even stopped the cancer growth long-term. In some cases the tumors disappeared completely.

Serotonin is a neurotransmitter - happiness hormone.

depressed people - serotonin in the brain is reduced.

Serotonin influences many other functions throughout the body. The majority of the serotonin is not located in the brain, but is stored in the blood platelets.

Serotonin reuptake inhibitors (SSRIs), which are used to treat depression, increase serotonin levels in the brain but decrease peripheral serotonin in platelets.

SSRIs slow tumor growth.

The involvement of serotonin in carcinogenesis known.

SSRIs or other drugs that lower peripheral serotonin levels can also slow cancer growth in mice.

serotonin plays role in this tumor cell resistance mechanism.

Without serotonin, the immune system recognizes the cancer cells again.

Cancer cells use serotonin to boost immunoinhibitory PD-L1. PD-L1 binds to killer T cells, —> dysfunctional.

SSRIs prevent this mechanism —> cause immune cells to eliminate tumor cells again.

PD-L1 - also the target of immunotherapies: immune checkpoint inhibitors.

If combine immunotherapy, which increases the activity of killer T cells, with drugs that reduce peripheral serotonin --> impressive: Cancer growth was suppressed in the animal models in the long term, and in some mice the tumors disappeared completely.