Agomelatine versus gefitinib against HepG2 cells: Modulating PI3K/AKT and MAPK/RAF1/c-FOS pathways.

Hepatocellular carcinoma (HCC) is the predominant form of cancer globally, characterized by a dismal prognosis and few treatment options. Agomelatine (AGO) acts as a melatonin receptor agonist and a 5-HT2C receptor antagonist, suggesting its potential anticancer efficacy across diverse cancer types. This study aims to assess the effects of AGO and gefitinib (GEF) on apoptosis, cell cycle, and caspase expression, and to examine their implications for the PI3K/AKT and MAPK/ERK pathways. The concentrations of AGO and GEF were altered in the cells. MTT tests (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) were used. A flow cytometry experiment was conducted after a single dose of AGO and GEF. The RT-qPCR test was used to assess the expression levels of caspases 8 and 9, as well as the PI3K/AKT and MAPK/RAF/c-FOS genes. AGO and GEF increased caspase expression, reduced cell viability, and induced apoptosis while inhibiting the expression of PI3K/AKT and MAPK/ERK genes. Our results demonstrated that both AGO and GEF impeded HCC progression by enhancing apoptosis and caspase expression while modulating the PI3K/AKT and MAPK/RAF/c-FOS signaling pathways, suggesting that AGO and GEF may serve as effective therapeutic options for HCC, with gefitinib exhibiting greater potential as an anticancer agent.