Fig Seed Oil Induces Mitochondrial-Mediated Apoptosis in HepG2 Cells

Year 2025, Volume: 32 Issue: 3, 230 - 239, 09.09.2025

Adem Yavaş

https://doi.org/10.17343/sdutfd.1682529

Abstract

Objective: Hepatocellular carcinoma (HCC) remains a significant global health challenge with limited effective therapies, necessitating the identification of novel therapeutic agents. Fig seed oil (FSO), rich in bioactive compounds, is being explored for its health benefits, including potential anti-cancer effects. This study investigated the cytotoxic, pro-apoptotic (via the mitochondrial pathway), and oxidative stress-modulating effects of FSO on HepG2 cells.
Material and Method: HepG2 cells were treated with FSO (0.1-1% v/v). Cell viability was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay over 24, 48, and 72 hours. Oxidative stress markers, including Total Antioxidant Status (TAS), Total Oxidant Status (TOS), and Oxidative Stress Index (OSI), were measured by ELISA. Key apoptotic proteins (Bax, Bcl-2, cytochrome c, cleaved caspase-9, and cleaved caspase-3) were evaluated using Western blot analysis.
Results: FSO demonstrated dose-dependent cytotoxicity against HepG2 cells, with an IC50 of 0.45% v/v at 72 hours. Treatment with 0.5% v/v FSO significantly improved cellular oxidative status by increasing TAS (1.8±0.2 vs 1.2±0.1 mmol Trolox eq/L, p<0.01), decreasing TOS (7.8±0.9 vs 12.4±1.3 µmol H2O2 eq/L, p<0.001), and consequently reducing the OSI by 58%. Furthermore, FSO induced mitochondrial apoptosis, evidenced by a 2.5-fold upregulation of Bax, a 60% decrease in Bcl-2, a 3.2-fold increase in cytosolic cytochrome c, a 2.8-fold increase in cleaved caspase-9, and a 3.1-fold increase in cleaved caspase-3 (p<0.05 for all significant changes).
Conclusion: This study shows that fig seed oil effectively induces mitochondrial-mediated apoptosis in HepG2 cells through caspase activation and simultaneously mitigates cellular oxidative stress. These findings suggest that FSO holds significant therapeutic potential for the treatment of hepatocellular carcinoma.

Keywords

Hepatocellular carcinoma , Fig seed oil , Apoptosis , Mitochondrial pathway , Oxidative stress

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