Citrus pectin oligomers in combination with cisplatin enhances apoptosis in HepG2 human hepatocellular carcinoma cells

Pectin is a widely used gelling agent in food, primarily composed of polygalacturonic acid. Cisplatin (DDP), a commonly used chemotherapeutic agent, has significant side effects, which necessitate efforts to reduce its usage. One approach to mitigate these side effects involves combining cisplatin with food-based bioactive compounds, such as oligogalacturonides (OGA) - shorter chain derivatives of pectin. In the present study, synergistic suppressive effects of OGA and DDP on hepatocellular carcinoma (HCC) cells were determined. HepG2 cells were treated with OGA (100 µg.ml-1) and DDP (2 µg.ml-1) in different combinations. Assays for cell viability, morphology, lactate dehydrogenase activity, cell cycle, apoptosis, western blot, galectin-3, and comet analysis were performed. Compared to DDP treatment, 55% reduction of IC50 values in the cell viability of HepG2 cells treated with DDP 12h + OGA 12h was observed. OGA-DDP combined showed the cell cycle arrest in G2/M, increased the galectin-3 release, and decreased the mitochondrial membrane permeability (MMP) significantly (p<0.05). Western blot study showed the upregulation of Bax, p53, and Caspase-3, and the downregulation of Bcl-2 proteins (p<0.05) by OGA and DDP combination treatment. These findings suggest that OGA-DDP enhances cisplatin’s anticancer efficacy while potentially reducing its required dosage, offering a promising strategy for improving HCC treatment outcomes.