Modulation of sphingolipid metabolism: Investigation of the apoptotic and cytotoxic effects of the ceramidase Inhibitor D-e-MAPP in HT29 colon cancer cells

Purpose: Colon cancer is one of the most common cancers of the digestive system and usually develops when polyps develop into cancer. Factors such as age, genetic predisposition and dietary habits increase the risk of the disease. Therefore, early diagnosis of colon cancer and development of appropriate clinical approaches are of great importance today. Sphingolipids are essential biological molecules that serve as important components of cell membranes and play important roles in various cellular processes. They are involved in various basic biological processes such as cell growth and differentiation, especially apoptosis (programmed cell death) and intracellular signaling. Sphingolipids are divided into different subgroups such as ceramide, sphingomyelin and glycosphingolipid and coordinate the design and activities of cells and play important roles in anticancer processes such as cell cycle arrest and inducing apoptosis. Dysfunction of sphingolipid metabolism plays a critical role in the development and progression of numerous cancers. Altered sphingolipid balance in cancer cells can affect the regulation of processes such as cellular growth, invasion and metastasis. In particular, changes in ceramide levels can activate cell survival pathways and cause cancer to become more aggressive. Method: In order to investigate the potential anticancer effects of ceramide inhibitor, we investigated the effects of D-e MAPP, a ceramidase inhibitor, on HT29 colon cancer cell line. For this purpose, cell viability and morphological changes after treatment were evaluated in detail. Cell viability was determined by MTT assay to determine the cytotoxic effects of treatment. Furthermore, structural and morphological changes in cells were visualized by confocal microscopy and treatment-induced cell death modes were determined by flow cytometry to obtain detailed information on cell death pathways. Findings: These methods aim to contribute to a more comprehensive understanding of the effects of ceramidase inhibitors on colon cancer cells. Conclusion: This study aims to contribute to a more comprehensive understanding of the effects of ceramidase inhibitors such as D-e-MAPP on colon cancer cells. By assessing cell viability, morphological changes and cell death pathways, this research provides valuable insights into the potential therapeutic applications of targeting sphingolipid metabolism in colon cancer treatment. Keywords: Colon cancer, sphingolipids, D-e-MAPP