Biomarker discovery using mass spectrometry (MS) has recently seen a significant increase in applications, mainly driven by the rapidly advancing field of metabolomics. Instrumental and data handling advancements have allowed for untargeted metabolite analyses which simultaneously interrogate multiple biochemical pathways to elucidate disease phenotypes and therapeutic mechanisms. Although most MS-based metabolomic approaches are coupled with liquid chromatography, a few recently published studies used matrix-assisted
laser desorption (MALDI), allowing for rapid and direct sample analysis with minimal sample preparation. We and others have reported that
prostaglandin E3 (
PGE3), derived from COX-2 metabolism of the
omega-3 fatty acid eicosapentaenoic acid (EPA), inhibited the proliferation of human lung, colon and
pancreatic cancer cells. However, how
PGE3 metabolism is regulated in
cancer cells, particularly human
non-small cell lung cancer (NSCLC) cells, is not fully understood. Here, we successfully used MALDI to identify differences in lipid metabolism between two human
non-small-cell lung cancer (NSCLC) cell lines, A549 and H596, which could contribute to their differential response to EPA treatment. Analysis by MALDI-MS showed that the level of EPA incorporated into
phospholipids in H596 cells was 4-fold higher than A549 cells. Intriguingly, H596 cells produced much less
PGE3 than A549 cells even though the expression of COX-2 was similar in these two cell lines. This appears to be due to the relatively lower expression of cytosolic
phospholipase A2 (cPLA2) in H596 cells than that of A549 cells. Additionally, the MALDI-MS approach was successfully used on
tumor tissue extracts from a K-ras transgenic mouse model of
lung cancer to enhance our understanding of the mechanism of action of EPA in the in vivo model. These results highlight the utility of combining a metabolomics workflow with MALDI-MS to identify the
biomarkers that may regulate the metabolism of
omega-3 fatty acids and ultimately affect their therapeutic potentials.