Chemotherapy-Induced Monoamine Oxidase Expression in Prostate Carcinoma Functions as a Cytoprotective Resistance Enzyme and Associates with Clinical Outcomes

Gordon, Ryan R.; Wu, Mengchu; Huang, Chung Ying; Harris, William Proctor; Sim, Hong Gee; Lucas, Jared M.; Coleman, Ilsa M.; Higano, Celestia S.; Gulati, Roman; True, Lawrence D.; Vessella, Robert L.; Lange, Paul H.; Garzotto, Mark; Beer, Tomasz M.; Nelson, Peter S.

doi:10.1371/journal.pone.0104271

Cited by 32 publications

(37 citation statements)

References 42 publications

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“…Together, these data suggest the involvement of MAOA in REST-mediated autophagy activation and NED in PCa. Since our data presented here demonstrates the up-regulation of MAOA in androgen deprivation-induced NE differentiated PCa cells and one recent study showed the induction of MAOA expression by chemotherapy34, we suggest that the addition of MAOA inhibitors may be a potential therapeutic for advanced PCa patients receiving combination ADT and chemotherapy.…”

Section: Discussionsupporting

confidence: 63%

MAOA-a novel decision maker of apoptosis and autophagy in hormone refractory neuroendocrine prostate cancer cells

Lin¹,

Chang²,

Campbell

et al. 2017

Sci Rep

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Autophagy and apoptosis are two well-controlled mechanisms regulating cell fate. An understanding of decision-making between these two pathways is in its infancy. Monoamine oxidase A (MAOA) is a mitochondrial enzyme that is well-known in psychiatric research. Emerging reports showed that overexpression MAOA is associated with prostate cancer (PCa). Here, we show that MAOA is involved in mediating neuroendocrine differentiation of PCa cells, a feature associated with hormone-refractory PCa (HRPC), a lethal type of disease. Following recent reports showing that NED of PCa requires down-regulation of repressor element-1 silencing transcription factor (REST) and activation of autophagy; we observe that MAOA is a novel direct target gene of REST. Reactive oxygen species (ROS) produced by overexpressed MAOA plays an essential role in inhibiting apoptosis and activating autophagy in NED PCa cells. MAOA inhibitors significantly reduced NED and autophagy activation of PCa cells. Our results here show MAOA as a new decision-maker for activating autophagy and MAOA inhibitors may be useful as a potential therapy for neuroendocrine tumors.

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Section: Discussionsupporting

confidence: 63%

MAOA-a novel decision maker of apoptosis and autophagy in hormone refractory neuroendocrine prostate cancer cells

Lin¹,

Chang²,

Campbell

et al. 2017

Sci Rep

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“…MAOA activity was found to be significant increased (p<0.05) in CSF of patients with acute lymphoblastic leukemia compared with control group as shown in tables (2) and (3) in both sexes for all age groups, this result was in agreement with other reports [27,28] who found evaluated levels of MAO in prostate cancer patients.…”

Section: -Monoamine Oxidase a (Maoa)supporting

confidence: 91%

Studying the Enzymes Levels in Cerebrospinal Fluid for Children With Acute Lymphoblastic Leukemia

Bdaiwi¹

2017

WJPPS

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The research includes studying of enzymes levels in the cerebrospinal fluid (CSF) for children with acute lymphoblastic leukemia (ALL) by determination of (9) parameter which include biochemical parameters: (73) were healthy children as control group which include (39) male and (34) female the age of children with acute lymphoblastic leukemia ranged from 1-15 year for both sex. The results showed there was a significant decrease in the activity of AChE, PChE and a significant increase in MAOA, AST, ALT, ALP, CK, LDH and SOD in CSF for children with acute lymphoblastic leukemia patients compared with control group for both sexes and these were a very good biochemical indicators for the patient body biochemical functions. The blood brain barrier loss its function in maintaining brain homoeostasis because of the oxidative stress and the age group (11-15)y of male had higher oxidative stress.

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“…Previously, investigators have reported a strong correlation between MAOA expression in tissue and the presence of high‐grade (Gleason patterns 4 or 5) prostate cancer . In addition, MAOA expression is associated with higher levels of serum prostate specific antigen (PSA) in patients at diagnosis . High MAOA expression in prostate cancer tissues correlated with worse clinical outcomes in patients .…”

Section: Introductionmentioning

confidence: 99%

Effect of Monoamine oxidase A (MAOA) inhibitors on androgen‐sensitive and castration‐resistant prostate cancer cells

et al. 2019

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Background: Monoamine oxidase A (MAOA) is best known for its role in neurotransmitter regulation. Monoamine oxidase inhibitors are used to treat atypical depression. MAOA is highly expressed in high grade prostate cancer and modulates tumorigenesis and progression in prostate cancer. Here, we investigated the potential role of MAOA inhibitors (MAOAIs) in relation to the androgen receptor (AR) pathway and resistance to antiandrogen treatment in prostate cancer. Methods: We examined MAOA expression and the effect of MAOI treatment in relation to AR-targeted treatments using the LNCaP, C4-2B, and 22Rv1 human prostate cancer cell lines. MAOA, AR-full length (AR-FL), AR splice variant 7 (AR-V7), and PSA expression was evaluated in the presence of MAOAIs (clorgyline, phenelzine), androgenic ligand (R1881), and antiandrogen (enzalutamide) treatments. An enzalutamide resistance cell line was generated to test the effect of MAOAI treatment in this model. Results: We observed that MAOAIs, particularly clorgyline and phenelzine, were effective at decreasing MAOA activity in human prostate cancer cells. MAOAIs significantly decreased growth of LNCaP, C4-2B, and 22Rv1 cells and produced additive growth inhibitory effects when combined with enzalutamide. Clorgyline decreased expression of AR-FL and AR-V7 in 22Rv1 cells and was effective at decreasing growth of an enzalutamide-resistant C4-2B cell line with increased AR-V7 expression. Conclusions: MAOAIs decrease growth and proliferation of androgen-sensitive and castration-resistant prostate cancer cells. Clorgyline, in particular, decreases expression of AR-FL and AR-V7 expression and decreases growth of an enzalutamideresistant cell line. These findings provide preclinical validation of MAOA inhibitors either alone or in combination with antiandrogens for therapeutic intent in patients with advanced forms of prostate cancer. K E Y W O R D S androgen receptor splice variant, clorgyline, enzalutamide, phenelzine, prostate cancer Shikha Gaur and Mitchell E. Gross are co-primary authors.

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Chemotherapy-Induced Monoamine Oxidase Expression in Prostate Carcinoma Functions as a Cytoprotective Resistance Enzyme and Associates with Clinical Outcomes

Cited by 32 publications

References 42 publications

MAOA-a novel decision maker of apoptosis and autophagy in hormone refractory neuroendocrine prostate cancer cells

MAOA-a novel decision maker of apoptosis and autophagy in hormone refractory neuroendocrine prostate cancer cells

Studying the Enzymes Levels in Cerebrospinal Fluid for Children With Acute Lymphoblastic Leukemia

Effect of Monoamine oxidase A (MAOA) inhibitors on androgen‐sensitive and castration‐resistant prostate cancer cells

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