Investigation of the connection of possible signal pathways with ceramidase inhibitor-mediated cytotoxicity in cancer cell arrays

Lung cancer is one of the most fatal cancer types in the world. The most common type of lung cancer is non-small cell lung cancer. Treatment of lung cancer and the development of safe and effective drugs with few side effects has become a focus in cancer research in recent years. Ceramidase inhibitors are shown as a potential new therapeutic class of antiproliferative and cytostatic drugs for use in cancer therapy. B13 (D-NMAPPD) is a potent acid ceramidase inhibitor that keeps the ceramide concentration high in cancer cells and promotes apoptosis. Nanoparticles, one of the new approaches in cancer treatments, have started to be used in the diagnosis and treatment of many diseases, and highly effective treatments can be developed thanks to the drug loaded nanoparticle forms. In the light of all this information, the purpose of our thesis is to investigate the cytotoxic, antiproliferative effects and cell death pattern caused by B13 and the newly synthesized SLN-B13 in lung cancer cell line in comparison with Beas-2B healthy lung cells. Cytotoxic effects of B13 and SLN-B13 on A549 and Beas-2B cells were determined by MTT and ATP tests and the determination of the type of death caused by cells was determined by flow cytometry. Afterwards, morphological changes in cells with confocal microscopy method and ultrastructural changes with permeable electron microscopy method were visualized. In addition, gene and protein expression levels of B13 and SLN-B13 were also determined. With this study, important results were obtained in the direction of examining the cytotoxic roles of B13 and SLN-B13 on the lung cancer cell line and explaining the cell death patterns with other methods. Keywords: B13, D-NMAPPD, Solid lipid nanoparticle, Lung cancer, Beas-2B