Anticancer effects of carmofur and its nano form on resistant breast cancer cells

Cancer is among the diseases with the highest mortality rates worldwide. Cancer is defined as a disease resulting from uncontrolled cell division caused by various factors. Recent research and applications generally focus on how sphingolipid metabolism and its modulation regulate the effective death of cancer cells as a new alternative to immunotherapy in cancer treatment. Carmofur, an inhibitor of acid ceramidase, has anticancer effects. Bortezomib, known for its proteasome inhibition and used in clinical treatment, modulates biological changes and triggers apoptosis. In this thesis, MCF-7 and bortezomib-resistant MCF-7 cells were propagated in cell culture. The toxicity of carmofur on MCF-7 and MCF-7/BOR cells was then calculated using the MTT cytotoxicity test. Morphological and ultrastructural changes between bortezomib- resistant and non-resistant MCF-7 cells treated with carmofur were compared using confocal and transmission electron microscopy (TEM). Carmofur Solid Lipid Nanoparticles were also synthesized and characterized, and the same experiments were performed for comparison. Intracellular ceramide levels were measured using LC- MS/MS. The effects of bortezomib-resistant cells were detected as cytoskeletal holes, fragmentation, and DNA strand breaks. All our results demonstrated that carmofur and its nanoform possess high cytotoxicity and anticancer potential, and that it is an effective therapeutic agent.