Work

Exogenous carnitine can modulate oxaliplatin sensitivity in colorectal cancer cells in vitro

Year: 2026

Type: article

Abstract: Objective The clinical management of colorectal cancer (CRC) is hampered by the frequent development of oxaliplatin (OXA) resistance. This study investigated whether exogenous L-carnitine (CAR) modulates OXA sensitivity in CRC cells and whether any such effect depends on fatty acid oxidation (FAO). Methods The effects of carnitine, with or without OXA, on cell viability, proliferation, migration, oxygen consumption, apoptosis, cell-cycle distribution, and intracellular reactive oxygen species (ROS) were evaluated in HCT116 parental cells and an OXA-resistant subline (HCT116/L), using CCK-8, colony formation, wound healing, Seahorse XF analysis, flow cytometry, and ROS fluorescence probes. Results In vitro , exogenous carnitine dose-dependently reduced CRC cell viability, proliferation, migration, and respiration, and promoted apoptosis. Co-treatment with carnitine partially attenuated the anti-proliferative and pro-apoptotic effects of OXA in HCT116/L cells, consistent with reduced chemosensitivity. This effect was accompanied by a partial restoration of fatty-acid-dependent respiration and a reduction in OXA-induced ROS accumulation. Conclusion In OXA-resistant HCT116/L (MSI-H) cells, exogenous carnitine is associated with reduced OXA sensitivity, an effect that requires fatty acid oxidation. These findings identify carnitine-FAO metabolism as a potential determinant of OXA response; whether limiting carnitine availability can restore OXA sensitivity in vivo remains a hypothesis to be tested.

Source: Frontiers in Pharmacology

DOI: 10.3389/fphar.2026.1963206