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Peer-reviewedCC BY 4.0Frontiers in Pharmacology

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

  1. 1Wenzhou Central Hospital
  2. 2Wenzhou Institute, University of Chinese Academy of Sciences

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.

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BibTeX
@article{fan2026exogenous,
  title = {{Exogenous carnitine can modulate oxaliplatin sensitivity in colorectal cancer cells in vitro}},
  author = {Yufang Fan and Jian Huang and Liqiang Dai and Lifeng Huang and Yuemiao Chen and Hongkai Cai and Qiuru Zhou and Wei Jiang and Ziyi Zhang and Xiaoping Cai and Yao-Gen Shu},
  journal = {Frontiers in Pharmacology},
  year = {2026},
  month = oct,
  doi = {10.3389/fphar.2026.1963206},
  url = {https://www.frontiersin.org/articles/10.3389/fphar.2026.1963206/full},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Exogenous carnitine can modulate oxaliplatin sensitivity in colorectal cancer cells in vitro
AU  - Yufang Fan
AU  - Jian Huang
AU  - Liqiang Dai
AU  - Lifeng Huang
AU  - Yuemiao Chen
AU  - Hongkai Cai
AU  - Qiuru Zhou
AU  - Wei Jiang
AU  - Ziyi Zhang
AU  - Xiaoping Cai
AU  - Yao-Gen Shu
PY  - 2026
DA  - 2026/10/28
JO  - Frontiers in Pharmacology
DO  - 10.3389/fphar.2026.1963206
UR  - https://www.frontiersin.org/articles/10.3389/fphar.2026.1963206/full
AB  - 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.
SN  - 1663-9812
ER  -