Combined inulin, glucomannan, and medium-chain triglyceride modulate metabolic and inflammatory responses in chemotherapy-treated colorectal cancer cells

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BSTRACT

Colorectal cancer (CRC) remains a global health challenge. The efficacy of 5-fluorouracil (5-FU) is frequently limited by chemoresistance, inflammation, and compensatory pro-angiogenic signaling. Prebiotic fibers and metabolically active lipids have been shown to modulate immune-metabolic pathways that may influence tumor behavior and chemotherapy response. The aim of the study was to evaluate the immunomodulatory and chemo-adjunct effects of inulin, glucomannan, and a combined inulin–glucomannan–medium-chain triglyceride (MCT) formulation on CRC cells exposed to 5-FU. An in vitro experimental study using human colorectal adenocarcinoma HT-29 cells. HT-29 cells were exposed to graded concentrations of inulin, glucomannan, or their combination with MCT, either as single treatments or combined with 5-FU. Outcomes included MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide)-based viability, clonogenic survival, and vascular endothelial growth factor (VEGF) and interleukin-6 (IL-6) expression using immunocytochemical (ICC). Data differences were analyzed using one-way analysis of variance with Tukey’s post hoc test or the Kruskal–Wallis test with Dunn’s post hoc test, as appropriate. Inulin increased short-term metabolic activity and partially attenuated 5-FU-induced cytotoxicity, whereas glucomannan demonstrated minimal effects. MCT supplementation further enhanced metabolic activity, indicating differential nutrient–chemotherapy interactions. The combined inulin–MCT–glucomannan formulation exerted the most consistent long-term effects, significantly reducing colony formation and modulating VEGF and IL-6 expression in a dose-dependent manner. However, VEGF increased at higher concentrations. The triple-component formulation modulated proliferative capacity and inflammatory-angiogenic signaling and altered cellular responses to 5-FU, supporting a modulatory rather than uniformly sensitizing role in CRC cells.