Synthetic Food Preservatives Modulate Apoptotic Gene Expression in HepG2 Cells: Divergent Effects of Sodium Benzoate, Potassium Sorbate, and Sodium Metabisulfite

<b>Background:</b> The accelerated lifestyle of modern society has increased reliance on processed foods preserved with synthetic additives. Although these substances effectively extend shelf life, several studies have raised concerns about potential adverse effects, suggesting that excessive or long-term exposure may interfere with essential cellular processes, including apoptosis. <b>Objectives:</b> This study aimed to investigate the impact of three widely used synthetic food preservatives; sodium benzoate (SB), potassium sorbate (PS), and sodium metabisulfite (SMB) on apoptosis-related gene expression in the human hepatocellular carcinoma cell line (HepG2). <b>Methods:</b> HepG2 cells were exposed to five increasing concentrations (6.25, 12.5, 25, 50, and 100 mg/L) of SB, PS, or SMB for 24 and 48 h. The transcriptional changes of key apoptotic genes (<i>CASP3</i>, <i>CASP8</i>, <i>BAX</i>, and <i>BCL2</i>) were quantified by real-time quantitative reverse transcription PCR (RT-qPCR) to evaluate their potential effects on intrinsic and extrinsic apoptotic pathways. <b>Results:</b> SB and PS induced dose-dependent transcriptional changes in apoptosis-related genes. Both preservatives upregulated <i>BAX</i> and downregulated <i>BCL2</i>, indicating an intrinsic pathway response, while simultaneously decreasing <i>CASP3</i> and <i>CASP8</i> expression associated with the extrinsic pathway. In contrast, SMB did not cause significant gene expression changes. <b>Conclusions:</b> SB and PS induced concentration- and time-dependent transcriptional alterations in apoptosis-related genes in HepG2 cells. In contrast, SMB did not elicit significant gene expression changes under the same conditions. These gene-level modulations were most evident at higher concentrations, which exceed typical dietary exposure levels. Therefore, while SB and PS were associated with transcriptional alterations at higher, experimentally relevant concentrations, additional research using primary human hepatocytes is needed to determine whether similar patterns occur in normal liver cells under physiological exposure conditions.