Investigation of ceramidase inhibition in cancer cells as a potential therapeutic target

Cancer cells are cells that divide and grow irregularly and have lost control of their ability to divide in a controlled manner. Normal cells grow, divide, and die in a controlled manner, but cancerous cells are different from normal cells and are dangerous. Cancer takes second order after cardiovascular diseases in terms of its prevalence in the world and in Turkey. Over 8 million people worldwide have been dying every year from cancer. Therefore, cancer has become a serious health problem. Lung cancer ranks first among cancer types in terms of its incidence. Although genetic factors are effective in the development of lung cancer, tobacco use is the biggest cause. Lung cancer is a cancer type with high lethality due to its ability to metastasize to many different organs such as the adrenal glands, liver, bone and brain. It is known that despite the advances in lung cancer treatment in recent years, a fully responsive treatment has not been achieved. Therefore, there is an unmet need for the development of safe and effective drugs to treat lung cancer and improve patients' quality of life during the treatment process. ARN14974 (BOC) is a ceramide inhibitor that causes the accumulation of ceramide in the cell and drives the cell into apoptosis. Ceramide is an important sphingolipid involved in the induction of apoptosis. Acid ceramidase is the enzyme that catalyzes the hydrolysis of ceramide to sphingosine and fatty acid. Acid ceramidase inhibition is known to affect the balance between cell proliferation and death by affecting both growth and survival of normal and neoplastic cells. In our study, we aimed to compare the cytotoxic, antiproliferative and apoptotic effects of ARN14974, a ceramide inhibitor, on non-small lung cancer cells (A549) and healthy epithelial lung cells (Beas-2B). Another aim of ours is to prevent the formation of ceramide-1-phosphate, which provides cell survival and proliferation and also inhibits apoptosis, and to investigate a new and effective treatment approach by increasing the intracellular level of ceramide.