Comparative Cytotoxic and Genotoxic Effects of Melatonin, Agomelatine and Ramelteon in U87-MG Glioblastoma and N2a Neuroblastoma Cells

Abstract

Purpose: While melatonin has been extensively investigated for its potential antitumor activity, the effects of its receptor agonists, agomelatin and ramelteon, on neural and glial tumour cells have not been sufficiently elucidated. This study aims to comparatively evaluate the cytotoxic and genotoxic effects of melatonin, agomelatin, and ramelteon on U87-MG glioblastoma and N2a neuroblastoma cells. Material and Methods: Cells were exposed to melatonin, agomelatin, and ramelteon at concentrations of 1, 5, 25, 50, and 100 µM for 24 hours. Cytotoxicity was assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) test, and genotoxicity was assessed using the comet test at half-maximum inhibitory concentrations. Results: According to the MTT results, all three compounds significantly reduced cell viability in U87-MG cells at all concentrations except 1 µM. In N2a cells, however, agomelatine and melatonin significantly reduced cell viability at all concentrations, whilst ramelteon caused a significant reduction only at concentrations of 50 and 100 µM. In the comet assay results, significant changes in parameters associated with DNA damage were observed in U87-MG cells with all three compounds. In N2a cells, whilst melatonin caused significant changes in parameters associated with DNA damage, agomelatin led to a significant reduction in cell density, and ramelteon did not induce any significant changes in the parameters assessed. The observed response patterns varied depending on the compound and cell type. Conclusion: These findings demonstrate that melatonin, agomelatin, and ramelteon exhibit different cytotoxic and genotoxic effects depending on the tumor cell type, highlighting their potential importance as candidate agents in neuro-oncological research.

Keywords

• agomelatine
• cancer
• glioblastoma
• melatonin
• neuroblastoma
• ramelteon

Supporting Institution

This research was funded by TÜBİTAK 2224-B (grant number 1919B022504145) and the Inonu University Scientific Research Projects Coordination Unit (project number TOA-2025-3973).

Project Number

TÜBİTAK 2224-B (1919B022504145), İNÜ-BAP (TOA-2025-3973)

Thanks

The authors would like to thank Inonu University Scientific Research Projects Coordination Unit and TÜBİTAK for their support of this study. The authors also sincerely thank their colleagues for their valuable technical assistance during the experimental procedures.

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