Abstract
Drug repurposing in oncology can reduce the time and cost of new drug development. Studies suggest that depression influences tumor progression, and some antidepressants exhibit anti-tumor effects. This study evaluated the effects of serotonergic antagonists-tropisetron, imipramine, ketanserin, and cyproheptadine-on AGS gastric cancer cells. The half-maximal inhibitory concentration (IC50) values of drugs were determined after 48 h in AGS cells using the MTT assay. Cell cycle distribution and apoptosis were evaluated by flow cytometry. Morphological changes were observed by Acridine Orange/Ethidium Bromide staining. The wound-healing assay was used to assess the effects of the drugs on cell migration. Real-time PCR was used to measure the expression of 5-hydroxytryptamine (5-HT) receptors (5-HT2A, 5-HT2B, 5-HT3A), serotonin transporter (SLC6A4/SERT), apoptosis-related genes (Bcl-2, Bax), and proliferating cell nuclear antigen (PCNA). All drugs significantly inhibited the growth of AGS cell in vitro. All four drugs induced apoptosis and inhibited cell migration with varying efficacies. Imipramine induced G1/S phase arrest, whereas tropisetron, ketanserin, and cyproheptadine increased the sub-G1 cell population. Gene expression analysis revealed decreased Bcl-2 and PCNA levels and increased Bax expression.These findings suggest the potential of tropisetron, imipramine, ketanserin, and cyproheptadine as repurposed therapeutic agents for gastric cancer.