Regulating Energy Metabolism to Induce the Release of VOC Biomarkers in Lung Cancer Cells

Early diagnosis of lung cancer is critical for improving patient outcomes. Noninvasive detection techniques based on volatile organic compounds (VOCs) are gaining attention due to their convenience and low risk. This study innovatively explores the application of dichloroacetate (DCA), a multifunctional small molecule, in lung cancer diagnosis by analyzing DCA-induced alterations in VOCs released from normal lung cells (BEAS-2B) and lung cancer cells (PC-9) using solid-phase microextraction coupled with gas chromatography-mass spectrometry (SPME-GC-MS). A DCA concentration of 5 mmol/L was selected to minimize adverse effects on normal cells. Results revealed that DCA induced distinct VOC profiles in normal and cancer cells, suggesting differential metabolic regulation. Concentration-gradient experiments demonstrated that 2-methyl-2-propanol release increased with DCA concentration in both cell types, but cancer cells responded only at higher concentrations. Acetoin level in cancer cells increased with DCA concentration, which was absent in normal cells. Similar results were observed in other lung cancer cell lines (A549 and NCI-H460), confirming reproducible DCA-induced VOC patterns. This study proposes a novel strategy combining DCA intervention with SPME-GC-MS to amplify cancer-specific VOC signatures, providing a promising foundation for breath-based early screening of lung cancer. The findings highlight the potential of metabolic modulation in enhancing noninvasive diagnostic technologies.