Effects of Serotonin, Granisetron, and Temozolomide Alone or in Combination on Neuroblastoma and Glial Cell Lines

Background: Neuroblastoma is the most common extracranial solid malignancy in infants and children. High-risk neuroblastoma patients are commonly treated with temozolomide (TMZ), which typically exhibits a poor therapeutic response. Serotonin, also known as 5-hydroxytryptamine (5-HT), plays various essential functions in the human body. In the central nervous system, it serves as a neurotransmitter. Beyond its physiological roles, 5-HT has recently been identified as a potential growth factor for several human tumors, including gliomas and carcinoid tumors. Recent literature has demonstrated that 5-HT receptor antagonists can inhibit the growth of cancer cells. Furthermore, both 5-HT receptors and their antagonists have been identified as potential anticancer agents, suggesting their significance in the development of new treatment strategies. Objectives: The primary aim of this study was to examine the effects of 5-HT and 5-HT antagonists on tumor (neuroblastoma (SH-SY5Y)) and healthy cells (microglia (HMC3)) and determine the impact of their interaction with the anticancer agent TMZ on cell proliferation/viability and migration. Methods: The study explored the interaction between 5-HT, the 5-HT antagonist granisetron (GRN), the anticancer agent TMZ, and their combinations, specifically assessing their influence on cell proliferation, viability, and migration. Results: As a result, the single and combined applications of 5-HT, TMZ, and GRN, a 5-HT antagonist, inhibited cell growth and proliferation in SH-SY5Y, causing decreased cell viability. Additionally, the combination of 5-HT and GRN increased the efficacy of TMZ. Conclusions: The study findings revealed that 5-HT and 5-HT antagonists may have therapeutic effects by exhibiting antiproliferative effects in SH-SY5Y cells at high concentrations.