PURPOSE: Inhibitors of monoamine oxidase A (MAOA), a mitochondrial enzyme that 
degrades neurotransmitters including serotonin and norepinephrine, are commonly 
used to treat neurological conditions including depression. Recently, we and 
others identified high expression of MAOA in normal basal prostatic epithelium 
and high-grade primary prostate cancer (PCa). In contrast, MAOA is low in normal 
secretory prostatic epithelium and low-grade PCa. An irreversible inhibitor of 
MAOA, clorgyline, induced secretory differentiation in primary cultures of 
normal basal epithelial cells and high-grade PCa. Furthermore, clorgyline 
inhibited several oncogenic pathways in PCa cells, suggesting clinical value of 
MAOA inhibitors as a pro-differentiation and anti-oncogenic therapy for 
high-risk PCa. Here, we extended our studies to a model of advanced PCa, VCaP 
cells, which were derived from castration-resistant metastatic PCa and express a 
high level of MAOA.
METHODS: Growth of VCaP cells in the presence or absence of clorgyline was 
evaluated in vitro and in vivo. Gene expression changes in response to 
clorgyline were determined by microarray and validated by quantitative real-time 
polymerase chain reaction.
RESULTS: Treatment with clorgyline in vitro inhibited growth and altered the 
transcriptional pattern of VCaP cells in a manner consistent with the 
pro-differentiation and anti-oncogenic effects seen in treated primary PCa 
cells. Src, beta-catenin, and MAPK oncogenic pathways, implicated in 
androgen-independent growth and metastasis, were significantly downregulated. 
Clorgyline treatment of mice bearing VCaP xenografts slowed tumor growth and 
induced transcriptome changes similar to those noted in vitro.
CONCLUSION: Our results support the possibility that anti-depressant drugs that 
target MAOA might find a new application in treating PCa.