Erbaş, Elif; Kara, Adem; Ustundag, Hilal; Albayrak, Kevser; Köse, Rukiye

This study investigated the combined effects of agomelatine, a melatonergic antidepressant, and cetuximab, an EGFR inhibitor, on the colorectal cancer cell line (Caco-2). Caco-2 cells were treated with agomelatine (0.3 μg/ml and 3 μg/ml) and cetuximab (50 μg/ml), individually and in combination, for 24 and 48 hours. Cell viability was assessed using the MTT assay. Gene expression analysis of EGFR, BCL2, PIK3CA, BAX, mTOR, and AKT3 was performed using real-time PCR. All treatment groups showed significant decreases in cell viability compared to the control (p<0.05), with enhanced effects in combined treatments. EGFR expression was significantly reduced in drug-treated groups, particularly with cetuximab (p<0.05). While changes were observed in BCL2, PIK3CA, BAX, mTOR, and AKT3 expression, these were not statistically significant (p>0.05). This study demonstrates the potential synergistic cytotoxic effects of agomelatine and cetuximab on Caco-2 colorectal cancer cells. The significant reduction in EGFR expression suggests a potential mechanism of action. These findings provide insights into combining chemotherapeutic agents with drugs addressing circadian rhythm disorders in CRC treatment strategies. Further research is warranted to elucidate the clinical implications of these observations.

Çıçek, Betül

Idebenone, an analogue of coenzyme Q10, may function as a neuroprotective agent with its antioxidant and anti-inflammatory properties. The current report was designed to examine the beneficial effects of idebenone on ethanol-related neurotoxicity in hippocampal neuronal HT-22 cells in vitro and annotate the neuroprotective mechanism of idebenone. 75 mM ethanol was applied to the cells for 24h to develop ethanol toxicity. Then, different concentrations of idebenone (final concentration in the well to be 1, 2.5, and 5 μM) were applied to HT-22 cells for 24 h to explore the protective impact against ethanol-induced hippocampal damage. Cell viability was evaluated with MTT test. MDA, SOD, and GSH concentrations were examined to interpret oxidative damage. Moreover, the effects of idebenone on IL-1β, IL-6, and IL-23 neuroimmune-related genes expression levels were assigned by the RT-PCR analysis. In our study, 75 mM ethanol decreased neuronal cell viability by approximately 61%. All concentrations of idebenone were not toxic to neurons. In addition, idebenone increased cell viability by reducing the damage caused by alcohol. Idebenone reversed the reduction in antioxidant capacity caused by ethanol through decreasing MDA and increasing SOD and GSH levels. In addition, idebenone attenuated ethanol-induced impairment in neuroimmune and neuroinflammatory responses by reducing IL-1β, IL-6, and IL-23 mRNA expression levels. Treatment with idebenone increased antioxidant capacity and a significant improvement was achieved in neuroimmune and neuroinflammatory parameters. Possible mechanisms underlying these beneficial effects cover the down-regulation of IL-1β, IL-6, and IL-23 receptors, and antioxidant restoration of idebenone.