Investigation of proapoptotic and anticancer effects mediated by intracellular ceramide changing dependent on ARN14974=BOC treatment in human non-small cell lung cancer

Kuş G., Vejselova Sezer C., Yaylacı Ö. K., Çömlekçi E., Kutlu H. M.

BIOLOGICAL DIVERSITY AND CONSERVATION, vol.165, no.2, pp.36-48, 2023 (Peer-Reviewed Journal)


Sphingolipids are structural molecules of cellular membranes, that regulate biological processes such growth, proliferation, migration, metastasis by controlling signaling functions of cancer cells. Recent research in cancer therapy has sought to find mechanical details of tumor growth and roles of sphingolipids and their downstream targets in chemotherapy, radiotherapy and/or immunotherapy responses, by innovative molecular and pharmacological tools targeting sphingolipid signaling nodes in cancer cells. Lung cancer is one of the most common cancers in our country and in the world. An important part of cancerderived deaths is lung cancer-derived. New and effective treatment modalities for lung cancer are increasingly needed. This research investigated the novel and effective treatment approach by inhibiting the formation of ceramidase1-phosphate, which inhibits apoptosis, with synthesis of solid lipid nanoparticles of the ceramidase inhibitorARN14974=BOC, thereby increasing the intracellular level of cell and promoting cell viability and proliferation. Results showed, cytotoxicity, antiproliferative effect, morphological and ultrastructural changes indicating apoptosis caused by ARN14974=BOC and its nanoparticle formulation on A549 cells. Apoptosis was induced by the agents via raising ROS, causing cell cycle arrest. The results underlined and prooved that cell death is trigered more effectively by the nanoparticle formulation of ARN14974=BOC on human non-small cell lung cancer cells.