New study below [1].
Don't be turned off by the title. The botton line is that a drug used as an anti-depressant might have a profound impact on PCa progression.
Monoamine oxidase [MAO] is an enzyme family with two members. The new paper is concerned with MAO-A, which breaks down serotonin, melatonin, norepinephrine, and epinephrine [2].
"Monoamine oxidase A (MAOA) is a mitochondrial enzyme, which degrades monoamine neurotransmitters and dietary amines and produces H2O2. Recent studies have shown increased MAOA expression in prostate cancer (PCa), glioma, and classical Hodgkin lymphoma. However, the biological function of MAOA in cancer development remains unknown. In this study, we investigated the role of MAOA in the development of prostate adenocarcinoma by creating a prostate-specific Pten/MAOA knockout (KO) mouse model ..."
In spite of being Pten-negative, the mice "exhibited a significant decrease in both prostate size and the incidence of invasive cancer."
A 2016 paper describes "Inhibitors of MAO-A and MAO-B in Psychiatry and Neurology" [3].
"Phenelzine (Nardil, Nardelzine) is a non-selective and irreversible monoamine oxidase inhibitor (MAOI) of the hydrazine class which is used as an antidepressant and anxiolytic. Along with tranylcypromine and isocarboxazid, phenelzine is one of the few non-selective and irreversible MAOIs still in widespread clinical use." [4]
"Tranylcypromine (... original trade name Parnate) is a monoamine oxidase inhibitor (MAOI); more specifically, tranylcypromine acts as nonselective and irreversible inhibitor of the enzyme monoamine oxidase (MAO). It is used as an antidepressant and anxiolytic agent in the clinical treatment of mood and anxiety disorders, respectively." [5]
In the context of PCa, a selective MAO-A inhibitor might be optimal:
Clorgiline (or Clorgyline): "is an irreversible and selective inhibitor of monoamine oxidase A (MAO-A). Clorgiline was never marketed, but it has found use in scientific research." [6] & was used in the study:
"... we found that Pten-positive PCa cells were more resistant to clorgyline treatments than Pten-null cells in tumorigenicity and stemness."
Loss of Pten makes management of PCa much more difficult, but it appears that Pten silencing is to our advantage when using a MAO-A inhibitor.
Conclusion: "MAOA expression promotes PCa development by increasing cell proliferation and {cancer stem cells} and highlights the potential use of MAOA inhibitors for the treatment of PCa."
Donna Peehl, back in 2009, came to a similar conclusion [7]:
"... inhibitors of MAO-A, already in clinical use to treat depression, may have potential application as therapeutic PCa drugs by inhibiting oncogenic pathway activity and promoting differentiation."
-Patrick
[1] nature.com/articles/s41388-...
[2] en.wikipedia.org/wiki/Monoa...
[3] ncbi.nlm.nih.gov/pmc/articl...
[4] en.wikipedia.org/wiki/Phene...
[5] en.wikipedia.org/wiki/Trany...
Metformin and hormonal resistance
