J Pharm Biomed Anal. 2025 Apr 23. pii: S0731-7085(25)00253-5. [Epub ahead of print]263 116912
Colorectal cancer (CRC), a common cancer of the large intestine, is influenced by metabolic reprogramming due to hypoxia. Novel biomarkers may be identified through metabolomics. While many CRC studies have reported metabolomic profiling, the metabolic profile of CRC in the context of oxygen content has yet to be elucidated. Comprehending the metabolic alterations in cancer cells transitioning from normoxia (NMX) to hypoxia (HPX) and anoxia (ANX) is essential for the formulation of drugs that target particular metabolic pathways. Our study aimed to find metabolic changes in the HCT-116 CRC cell line under ANX, HPX, and NMX conditions, as well as to investigate novel biomarkers for CRC utilizing liquid chromatography-mass spectrometry (LC-MS/MS) based metabolomics approaches. Our findings showed significant changes in 77 metabolites in HCT-116 CRC cells across ANX, HPX, and NMX conditions, with 34 metabolites significantly disrupted in HPX compared to NMX, and 64 metabolites significantly changed in HPX compared to ANX. Significant differences included glutathione, gamma-glutamylcysteine, glycerophosphocholine, adenosine monophosphate, 5'-methylthioadenosine, guanosine 5'-diphosphate, threonic acid, and L-acetylcarnitine. Comprehending the metabolic changes in HPX, ANX, and NMX may uncover new pathways that could be targeted for potential treatments.
Keywords: Biomarkers; Colorectal cancer; Hypoxia; LC-MS/MS; Metabolomics