Volatilomic Signatures of Parental and Oxaliplatin-Resistant HCT116 Colon Cancer Cell Lines

Volatile organic compounds (VOCs) reflect cellular metabolic activities and may serve as non-invasive biomarkers in oncology. This study investigated whether acquired oxaliplatin resistance in colorectal cancer is associated with distinct volatilomic alterations. The human colorectal cancer cell line HCT116 and its oxaliplatin-resistant derivative (OXrHCT116) were analyzed under basal conditions and following oxaliplatin exposure. Chemoresistance was confirmed using dose-response, cell viability, and colony formation assays. VOCs were analyzed by headspace needle trap extraction coupled with gas chromatography-mass spectrometry (HS-NTE-GC-MS). OXrHCT116 cells exhibited markedly reduced oxaliplatin sensitivity, increased IC₅₀ values, and reduced proliferative and clonogenic capacity. Volatilomic profiling identified 55 significantly altered VOCs. Parental HCT116 cells displayed broader VOC diversity and higher turnover than OXrHCT116 cells. Hydrocarbons associated with lipid peroxidation and oxidative stress were more abundant in HCT116 cells, whereas resistant cells showed markedly reduced emission of these compounds. Additional alterations in aldehydes, alcohols, and aromatic compounds suggested reduced metabolic flux in resistant cells. Oxaliplatin exposure induced pronounced volatilomic changes in HCT116 cells but only minimal modulation in OXrHCT116 cells. These findings suggest that oxaliplatin resistance may be associated with distinct metabolic reprogramming and support VOC profiling as a promising approach for monitoring chemoresistance.