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Agomelatine versus gefitinib against HepG2 cells: Modulating PI3K/AKT and MAPK/RAF1/c-FOS pathways
Heba M Abd El Kareem1, Sara F Saadawy2, Mai M ELdaly2
1Department of Biochemistry and Molecular Biology, Faculty of Medicine, Benha University, Benha, 13511, Egypt.
Background:
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.
Aim:
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.
Methods:
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.
Results:
AGO and GEF increased caspase expression, reduced cell viability, and induced apoptosis while inhibiting the expression of PI3K/AKT and MAPK/ERK genes.
Conclusion:
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.
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