| Background and Aims: Resistance to 5-fluorouracil (5-FU) is a significant challenge in the treatment of colorectal cancer. Metabolic factors in the tumor microenvironment, such as elevated glucose concentration, contribute to this resistance. This study aimed to evaluate the effects of honey with different PAD scores (Phenolic level, Antioxidant level, Diastase activity) on HT-29 cell response to 5-FU and their association with lactate dehydrogenase (LDH) activity and glucose consumption. Materials and Methods: In this in vitro study, HT-29 cells were cultured under two conditions: normal glucose (Normal Glc) and high glucose (High Glc). Experimental groups included: 5-FU alone; 5-FU combined with High-PAD score and Low-PAD score honey; honey alone (High-PAD score and Low-PAD score); untreated controls; and 5-FU under High Glc. The MTT assay assessed cell viability, while glucose consumption and LDH activity were measured using commercial kits. All experiments were performed in triplicate. Statistical analyses were conducted using SPSS software (version 19) using one-way ANOVA and t-tests (P≤0.05). Results: The IC50 of 5-FU increased 2.2-fold in High Glc (110 μM), compared to Normal Glc (50 μM). In Normal Glc, combining 5-FU with High-PAD score and Low-PAD score honey reduced the IC50 to 25 μM. The highest normalized LDH activity (0.8226±0.0096) and the most significant decrease in extracellular glucose (10±1.41 mg/dL) were observed in the 5-FU+High-PAD score honey group. The High Glc control exhibited elevated LDH (~0.83) but much higher residual glucose (298.5 mg/dL). Conclusion: Co-administration of 5-FU with honey, particularly high-PAD score honey, can mitigate drug resistance, likely by increasing glucose consumption and LDH activity. |
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