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Background <p>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.</p> Aim <p>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 <i>PI3K/AKT and MAPK/ERK</i> pathways.</p> Methods <p>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 <i>PI3K/AKT and MAPK/RAF/c-FOS</i> genes.</p> Results <p>AGO and GEF increased caspase expression, reduced cell viability, and induced apoptosis while inhibiting the expression of <i>PI3K/AKT and MAPK/ERK</i> genes.</p> Conclusion <p>Our results demonstrated that both AGO and GEF impeded HCC progression by enhancing apoptosis and caspase expression while modulating the <i>PI3K/AKT and MAPK/RAF/c-FOS</i> signaling pathways, suggesting that AGO and GEF may serve as effective therapeutic options for HCC, with gefitinib exhibiting greater potential as an anticancer agent.</p>

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

  • 期刊论文

  • 发表日期：

    2026年7月16日

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  • Heba M. Abd El Kareem,
  • Sara F. Saadawy,
  • Mai M. ELdaly,
  • Yousef Al-Saraireh,
  • Heba A. Hassan

摘要

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.