Clorgyline treatment of VCaP cells

ABSTRACT: Purpose: Monoamine oxidase A (MAOA) is a mitochondrial enzyme that degrades neurotransmitters including serotonin and norepinephrine. Its inhibitors are commonly used to treat neurologic conditions including depression. Recently, we and others identified high expression of MAOA in normal basal prostate epithelium and in high grade primary prostate cancer (PCa). Inhibition of MAOA with an irreversible inhibitor, clorgyline, induced differentiation in primary cultures of epithelial cells from normal tissues and high grade cancers. Furthermore, clorgyline treatment inhibited several oncogenic pathways in PCa cells, suggesting a 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: The 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 PCR. 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. Conclusions: Our results support the possibility that anti-depressant drugs that target MAOA might find a new application in treating PCa. Compound Based Treatment: Clorgyline treament of VCaP cells

ORGANISM(S): Homo sapiens

PROVIDER: GSE19822 | GEO | 2010/10/25

SECONDARY ACCESSION(S): PRJNA122149

REPOSITORIES: GEO