Lipidomics analysis of ceramidase inhibition-induced intracellular lipid profile changes in lung cancer cells

Lung cancer is among the most prevalent types of cancer globally and in Türkiye. Basically, lung cancer is divided into 2 different types, of which non-small cell lung cancer (NSCLC) accounts for about 85% of cases. With the elucidation of the mechanism of NSCLC, there is an urgent need to identify effective non-toxic drugs and new target biomarkers. Therefore, an immediate need exists to clarify the mechanism of NSCLC and identify effective, nontoxic drugs and novel target biomarkers. In this study, we aimed to determine intracellular lipid level changes caused by N-Oleoylethanolamine (NOE) and N-Oleoylethanolamine Solid Lipid Nanoparticle (NOESLN) formulations in test cell lines determined by mass spectrometry LC-MS/MS lipidomic analysis. Lipid level changes induced by N-Oleoylethanolamine (NOE) and N-Oleoylethanolamine Solid Lipid Nanoparticle (NOESLN) formulations in test cell lines have been determined by mass spectrometry LC-MS/MS lipidomics analysis. The particle size of the nanoparticle formulation was found to be 100 times smaller compared to the NOE particle size. According to MTT results, IC₅₀ values obtained in Beas-2B and A549 cells treated with NOE were higher than those treated with NOESLN. It was found that an raise in intracellular ceramide concentrations due to ceramidase inhibition can cause apoptotic death of cancer cells in A549 cells induced by N-Oleoylethanolamine (NOE), a unique inhibitor of ceramidase enzymes, and a newly synthesized solid lipid nanoform. This study demonstrates that NOE-loaded solid lipid nanoparticles (NOESLN) significantly enhance cytotoxic effects in NSCLC cells by inducing intracellular ceramide accumulation, suggesting their potential as effective and novel therapeutic agents for lung cancer treatment.