Relationship between anticancer sensitivities and cellular respiration properties in 5‐fluorouracil‐resistant HCT116 human colorectal cancer cells

• Published in: FEBS open bio Vol. 13; no. 6; pp. 1125 - 1133
• Main Authors: Kurasaka, Chinatsu, Nishizawa, Nana, Uozumi, Haruka, Ogino, Yoko, Sato, Akira
• Format: Journal Article
• Language: English
• Published: England John Wiley & Sons, Inc 01.06.2023; John Wiley and Sons Inc; Wiley
• Subjects: 5-Fluorouracil; Acidification; Adenosine Triphosphate - metabolism; Cell growth; Cell Respiration; cellular respiration; Chemotherapy; Colorectal Cancer; colorectal cancer cell; Colorectal carcinoma; Colorectal Neoplasms - drug therapy; Colorectal Neoplasms - metabolism; Drug Resistance; Drug Resistance, Neoplasm; Electron transport; Enzymes; Fluorouracil - pharmacology; Gene amplification; Glucose; glucose restriction; Glycolysis; HCT116; HCT116 Cells; Humans; Metabolism; Metabolites; Mitochondria; Respiration; Sensitivity analysis; Variance analysis; United States > US; Japan; 5-fluorouracil; glucose restriction; HCT116; cellular respiration; drug resistance; colorectal cancer cell
• ISSN: 2211-5463; 2211-5463
• DOI: 10.1002/2211-5463.13611

5‐Fluorouracil (5‐FU) is widely used for colorectal cancer (CRC) treatment; however, continuous treatment of CRC cells with 5‐FU can result in acquired resistance, and the underlying mechanism of 5‐FU resistance remains unclear. We previously established an acquired 5‐FU‐resistant CRC cell line, HCT116RF10, and examined its biological features and 5‐FU resistance mechanisms. In this study, we evaluated the 5‐FU sensitivity and cellular respiration dependency of HCT116RF10 cells and parental HCT116 cells under conditions of high‐ and low‐glucose concentrations. Both HCT116RF10 and parental HCT116 cells were more sensitive to 5‐FU under low‐glucose conditions compared with high‐glucose conditions. Interestingly, HCT116RF10 and parental HCT116 cells exhibited altered cellular respiration dependence for glycolysis and mitochondrial respiration under high‐ and low‐glucose conditions. Additionally, HCT116RF10 cells showed a markedly decreased ATP production rate compared with HCT116 cells under both high‐ and low‐glucose conditions. Importantly, glucose restriction significantly reduced the ATP production rate for both glycolysis and mitochondrial respiration in HCT116RF10 cells compared with HCT116 cells. The ATP production rates in HCT116RF10 and HCT116 cells were reduced by approximately 64% and 23%, respectively, under glucose restriction, suggesting that glucose restriction may be effective at enhancing 5‐FU chemotherapy. Overall, these findings shed light on 5‐FU resistance mechanisms, which may lead to improvements in anticancer treatment strategies. Glucose restriction enhanced 5‐FU chemotherapy and reduced the ATP production rate for both glycolysis and mitochondrial respiration in 5‐FU‐resistant HCT116R cells and parental HCT116 cells.