Serotonin synthesis and metabolism-related molecules in a human prostate cancer cell line

Abstract

Abstract. Prostate cancer is one of the most common tumors in males and its incidence is steadily increasing worldwide. Serotonin or 5-hydroxytryptamine (5-HT) is a well-known neurotransmitter that mediates a wide variety of physiological effects. An increase in the number of 5-HT-releasing neuroendocrine (NE) cells has been correlated with tumor progression. However, it is particularly unclear whether released 5-HT or the release of 5-HT has a role in tumor cell growth. We hypothesized that 5-HT synthesis and metabolism in NE cells regulate the growth of prostate cancer cells. In the present study, 5-HT was found to play a role as a cell growth factor in prostate cancer cells. Moreover, the pharmacological inhibition of 5-HT synthesis and metabolism interrupted the growth of prostate cancer cells. To confirm the existence of 5-HT in prostate cancer cells, we performed ELISA, HPLC, RT-PCR and immunohistochemical analyses. A high expression of tryptophan hydroxylase (TPH-1), dopa decarboxylase (DDC) and monoamine oxidase A (MAO-A) was noted in the prostate cancer cells when compared with normal prostate cells. Previous studies showed that 5-HT stimulated the proliferation of prostate cancer cells mediated by 5-HT receptors 5-HTR1A and R1B. However, cell proliferation was significantly inhibited when siRNA for both DDC and TPH-1 was transfected to the cells. Consequently, we propose that the secretion system of prostate NE cells capable of 5-HT synthesis and metabolism plays a significant role in prostate tumor generation and progression. These findings provide crucial clues for the development of potential pharmacotherapeutics to slow prostate tumor progression.

Dual inhibition of survivin and MAOA synergistically impairs growth of PTEN-negative prostate cancer

“…Consistent with the recent finding that increased MAOA expression in PCa promoted EMT ( Wu et al , 2014 ), our data further showed that MMP-9 mediates MAOA-induced PCa metastasis. In addition, the evidence that both increased MAOA expression and the addition of 5-HT ( Shinka et al , 2011 ) promoted PCa progression suggests that the direct and/or indirect metabolic products of MAOA contribute to PCa growth. Future studies will be needed to further elucidate the mechanisms.…”

“…Therefore, MAOA has been extensively studied in neurological disorders, such as Parkinson's disease and depression ( Youdim et al , 2006 ). Interestingly, an increase in the number of 5-HT-releasing neuroendocrine cells has been correlated with tumour progression, and 5-HT serves as a growth factor for PCa cells ( Shinka et al , 2011 ). In addition, elevated expression of MAOA correlates with high-grade PCa, and contributes to its poorly differentiated phenotype ( Vaarala et al , 2000 ; True et al , 2006 ; Peehl et al , 2008 ; Zhao et al , 2008 ).…”

Enhanced anticancer activity of a combination of docetaxel and Aneustat (OMN54) in a patient‐derived, advanced prostate cancer tissue xenograft model

“…The gene expression analysis also suggests stimulation of serotonin degradation as another action of Aneustat (Table 1). Studies have shown that growth of prostate cancer cells can be interrupted by inhibiting the synthesis and metabolism of serotonin, a neurotransmitter that plays a role as a growth factor for prostate cancer cells (Dizeyi et al., 2011; Shinka et al., 2011). Additional experimental verification will be needed to establish these mechanistic properties of Aneustat.…”

Increased risk for urological cancer associated with anxiety disorder: a retrospective cohort study

“…Lines of evidence suggest that persistent activation of the hypothalamic-pituitary-adrenal (HPA) axis can alter the function of the neuroendocrine system, disrupt the circadian glucocorticoid rhythm, and thus promote tumor initiation and progression [28–31]. More specifically, stress-related neurotransmitters such as serotonin were proposed as being correlated with the progression of urological cancers [32, 33]. …”