A few years ago, I did a post on the strikingly positive effects in-vivo of the dopamine agonist and (partial) serotonin antagonist bromocriptine (a member of the ergot class) in breast cancer. Using both native tumors and human tumors transplanted into rodents, bromocriptine achieved ~50%+ cure rates – i.e. primary tumor and metastases completely regressed and did not recur. My though at the time was that this was solid evidence that breast cancer is caused (and promoted) by estrogen, and since anti-prolactin drugs are de-facto anti-estrogenic, the effects of bromocriptine are hardly surprising.
https://pubmed.ncbi.nlm.nih.gov/327183/
http://www.ncbi.nlm.nih.gov/pubmed/6416848
At the time I had a few exchanges with doctors about that post, some of whom were oncologists. Their take was that since bromocriptine is a “dirty drug” (has multiple mechanisms of action) one cannot claim that it was bromocriptine’s anti-estrogenic effects that are solely responsible. And guess what? They were right…but for the wrong reasons! Since then, I discovered a multitude of studies demonstrating serotonin (5-HT) is both a cause and promoter of cancer, and that dopamine can activate the progesterone receptors. In other words, bromocriptine works by antagonizing estrogen and serotonin and promoting progesterone signalling, with the final conclusion being that estrogen/serotonin cause and promote cancer, while progesterone/dopamine are therapeutic. The study below corroborates this hypothesis by demonstrating that another drug, with much more selective pro-dopamine effects, is also therapeutic for breast cancer. And unlike the studies above, which used only estrogen-sensitive cancers, the study below found that the dopaminergic drug was effective against all types of breast cancer, including the dreaded triple-negative type (TNBC). The drug of note is our old friend selegiline (Deprenyl), which has acquired notoriety worldwide as being the anti-aging drug of choice of the elite for decades…and the only one so far proven to work in humans for anti-aging purposes. Selegiline’s sole known mechanism of action is being a monoamine oxidase B (MAO-B) inhibitor. Considering getting access to this drug is hard (and bound to become even harder considering its therapeutic potential), it would be helpful if one could use another MAO-B inhibitor not subject to the same notoriety/restrictions. Luckily, naphthoquinones such as vitamin K and the the main constituent of clove oil known as eugenol are also potent and selective MAO-B inhibitors.
https://pubmed.ncbi.nlm.nih.gov/22071524/
“…Herein we show that MAO-B was inhibited competitively by 1,4-NQ (K(i)=1.4 μM) whereas MAO-A was inhibited by non-competitive mechanism (K(i)=7.7 μM). Contrasting with TMN and 1,4-NQ, menadione (vitamin K3) exhibited a 60-fold selectivity for MAO-B (K(i)=0.4 μM) in comparison with MAO-A (K(i)=26 μM), which makes it as selective as rasagiline.”
https://onlinelibrary.wiley.com/doi/abs/10.1111/jfbc.13571
“…The phytoconstituents were investigated for their MAO-B inhibitory activity by an in vitro fluorimetric assay. The phytoconstituents were tested to inhibit the MAO-B enzyme at two different concentrations, 10μM and 40μM. It was observed that eugenol showed the maximum inhibition of 21.48± 0.059% and 63.11± 2.95% at 10μM and 40μM concentration, respectively. Whereas piperine showed inhibition of 13.32± 3.91% and 37.19± 12.21% at 10μM and 40μM concentration, respectively. The reference drug selegiline, which is a known inhibitor of MAO-B, showed 84.63± 4.32% and 85.30± 2.92% inhibition at 10μM and 40 μM concentration, respectively (Figure 3a).”
All in all, the evidence continues to accumulate that pro-metabolic, anti-estrogenic, anti-serotonin, progestogenic and dopaminergic pathways are highly beneficial not only for a large number of very serious degenerative conditions, but they make one slim, happy, frisky (due to the antiprolactin effects) and long-living. And since estrogenic (PUFA, birth control, endocrine disruptors, etc) and serotonergic (SSRI) substances functionally approximately opposite to selegiline, you can imagine what their effects are.
https://pib.gov.in/PressReleasePage.aspx?PRID=2050881
“…This research group has shown that Selegiline (L-deprenyl), an antidepressant drug from a class of drugs called monoamine oxidase (MAO) inhibitors, might be applied as anticancer therapeutics for breast cancer. The integrated network pharmacological studies found that selegiline interacts with ten genes intricately linked to various types of cancer, with a significant number of nodes. The study conducted a preliminary comparative evaluation of the efficacy of selegiline on six cancer cell lines. Selegiline was found effective in killing estrogen and progesterone-positive (ER+ & PR+) as well as triple-negative breast cancer (TNBC).”
