The effect of serotonin and serotonin antagonists on bladder cancer cell proliferation

Abstract

cancer tissue was determined by immunohistochemistry and Western blot analysis. RESULTS5HT caused a dose-dependent increase in the proliferation of HT1376 cells. The maximum increase in cell proliferation (12%; 12 samples, P < 0.001) was at 10 − 8 M as compared to the control at 72 h. At 10 − 4 M , 5HT 1A antagonist and 5HT 1B antagonist (SB224289 hydrochloride) had a 10% (12 samples, P < 0.001) and 93% (12, P < 0.001) inhibitory effect on HT1376 cell growth, respectively, compared to the control at 72 h. There was immunostaining for 5HT 1A and 5HT 1B receptors in HT1376 cells and malignant bladder tissue, confirming the presence of these two receptor subtypes. Western blot analysis showed the presence of 5HT 1A and 5HT 1B receptor proteins with bands of 46 kDa and 43 kDa, respectively. CONCLUSION5HT 1A and to a greater extent 5HT 1B antagonists significantly inhibit bladder cancer cell growth. This effect is probably mediated via the 5HT 1A and 5HT 1B receptors. These results highlight the potential use of 5HT 1A and 5HT 1B antagonists in the treatment of bladder cancer.

Serotonin Regulates Macrophage-Mediated Angiogenesis in a Mouse Model of Colon Cancer Allografts

“…Serotonin was previously shown to be mitogenic in different cancer cell lines (13)(14)(15). In line with these reports, colon cancer cell lines CT-26 and MC-38 showed increased proliferative activity when exposed to serotonin in vitro.…”

“…Accordingly, antagonists for serotonin receptors 1A and 1B reduced the proliferation rate of bladder cancer cells in vitro (15). However, in vivo studies investigating the function of serotonin in cancer growth and progression are lacking.…”

Anti-mitogenic and apoptotic effects of 5-HT1B receptor antagonist on HT29 colorectal cancer cell line

“…The mitogenic eVect of 5-HT on HT29 cells may be dependent on the presence of serum and its interaction with other hormones or growth factors (Sharpe et al 2002;Sonier et al 2006). In support of our study, previous investigations have suggested that 5-HT increases the growth rate of HT1376 bladder cancer cells (Siddiqui et al 2006) and human prostate cancer cells (Dizeyi et al 2004). Another study has shown that the proliferative properties of 5-HT may occur due to its binding to diVerent 5-HT receptor subtypes which are associated with cascades of mitogenic signaling pathways (Launay et al 1996).…”

“…After calculating immunoreactivity index of the receptors for each patient, we calculated mean and SD of 30 patients. Data analysis was carried out using Student's t test (Bradford 1976;Dizeyi et al 2004;Siddiqui et al 2006). …”

“…Serotonin (5-hydroxytryptamine, 5-HT) is a neurotransmitter that mediates a wide variety of physiological eVects including peripheral and central action through the binding of multiple receptor subtypes (Wilkinson and Dourish 1991). Although the mitogenic eVects of serotonin receptors, especially 5-HT 1A , 5-HT 1B , 5-HT 1D and 5-HT 2A , in breast cancer, prostate cancer and bladder cancer have been investigated (Dizeyi et al 2004;Siddiqui et al 2006;Sonier et al 2005Sonier et al , 2006, there is a lack of evidence about whether these receptors play a signiWcant role in colorectal cancer.…”