Serotonin and Melatonin Do Not Play a Prominent Role in the Growth of Prostate Cancer Cell Lines

Abstract

Objectives: To investigate the effects of serotonin and melatonin (MLT) on the regulation of malignant growth and the activity of serotonin receptors (5HTR1a/-1b) in prostate cancer (PCa) cell lines. Materials and Methods: In four PCa cell lines (LNCaP, 22RV1, PC3, DU145) and two reference cell lines 5HTR1a and -1b, relative mRNA expression levels were assessed. Different serotonin and MLT receptor agonists and antagonists were used in stimulation and inhibition experiments. Results: mRNA expression of 5HTR1b was higher than that of 5HTR1a in all PCa cell lines. Serotonin showed a significant growth stimulatory effect in all PCa lines. The 5HTR1a and -1b agonists/antagonists did not significantly affect viability. MLT inhibited viability only in PC3 cells. Similarly, the 5HTR1a antagonist induced apoptotic changes in PC3 cells only at 10^–4M, while the 5HTR1b antagonist induced necrosis at 10^–4M in all cell lines. Cell cycle alterations were seen in PC3 and DU145 cells under the influence of the 5HTR1a antagonist. Conclusions: Serotonin receptor antagonists and agonists as well as MLT influence viability and apoptosis of PCa cell lines at supraphysiologic concentrations. In contrast to other reports, our results do not support a regulatory role of serotonin or MLT receptor activation or inhibition in PCa growth.

Night Shift Work and Levels of 6-Sulfatoxymelatonin and Cortisol in Men

“…Recently, Blask and colleagues conducted a series of experiments which demonstrated directly the inverse relationship that exists between melatonin level and tumor activity, using both steroid receptor-positive and negative human breast cancer xenografts in rats; (44;45); the same team has since demonstrated similar results with prostate cancer xenografts (46). Other studies have reported a reduction in growth of malignant prostate tumor cells by both pharmacological and physiologic doses of melatonin (47-55), although such findings are not always consistent (56;57). The present study found that night shift work is associated with lower urinary 6-sulfatoxymelatonin levels during night work and daytime sleep, and that levels remain low even during night sleep on off-nights.…”

Monoamine oxidase A mediates prostate tumorigenesis and cancer metastasis

“…Moreover, we also nin in cholangiocarcinoma, which stimulate cholangiocarcinoma cell growth, and this condition is responsive to the blockade by the inhibition of serotonin synthesis (50,52). In contrast, serotonin by itself plays a marginal role in regulating the growth of PCa cells in general (53), and there was no significant clinical correlation of serotonin levels with PCa disease progression (54,55). The different effects of serotonin in diverse cancers therefore also provide insights into the differential functions of MAOA in PCa and other cancers.…”

Serotonin and ionizing radiation synergistically affect proliferation and adhesion molecule expression of malignant melanoma cells

“…Effects of serotonin on human tumour cells have been evaluated by several authors in recent years [13,[43][44][45][46][47]; however, it has remained controversial whether, in this context, serotonin promotes or inhibits tumour growth. In the present study we detected that serotonin dose-dependently inhibited cell growth of IPC-298 melanoma cells.…”

“…In contrast, serotonin has been reported to act as a growth factor for several types of human cancer, e.g. prostate carcinoma, lung carcinoma, colonic carcinoma and starved hepatocellular carcinoma cells [13,[45][46][47]. Most often the stimulatory effect of serotonin has been considered to be related with the specific vasoconstrictive effect of 5HT or 5HT2 agonists on the vessels irrigating the tumour [13].…”