title: Examining impacts of ceranib-2 on the proliferation, morphology and ultrastructure of human breast cancer cells.
abstract: Acid ceramidases are enzymes with a vital role in metabolizing ceramide to sphingosine-1-phosphate that is an antiproliferative metabolite in the ceramide pathway. Inhibition of exogenous ceramides with ceramidase inhibitors lead to augmented ceramide levels in cells and in turn lead to cell cycle arrest and apoptosis. Our study aimed at targeting ceramide metabolic pathway to induce apoptosis in human breast cancer cell line (MCF7) and we examined the antiproliferative and apoptotic activities of ceranib-2, an inhibitor of human ceramidase, on this cell line as well ultrastructural and mophological changes. Methods used for our examinations in this study were the colorimetric MTT assay, Annexin V/Propidium iodide and JC-1 staining, transmission electron microscopy and confocal microscopy. Ceranib-2 effectively inhibited the viability of MCF7 cells in 24 h in a dose dependent manner leading to apoptosis via the mitochondrial pathway by reducing the potential of mitochondrial membrane. Additionally, significant changes on cell morphology and ultrastructure were observed on MCF7 cells exposed to ceranib-2 indicating apoptotic cell death. Collectively, our data demonstrate that ceranib-2 exerts a great potential to be an antineoplastic compound and that the mechanism of its action rely on its apoptosis inducing ability.
authors.affiliation: Department of Biology, Faculty of Science, Anadolu University, Yunusemre Campus, Tepebasi, 26470, Eskisehir, Turkey. cananveyselova@gmail.com.
authors.forename: Djanan
authors.initials: D
authors.lastname: Vejselova
authors.affiliation: Department of Biology, Faculty of Science, Anadolu University, Yunusemre Campus, Tepebasi, 26470, Eskisehir, Turkey.
authors.forename: Hatice Mehtap
authors.initials: HM
authors.lastname: Kutlu
authors.affiliation: Department of Health, Faculty of Open Education, Anadolu University, Eskisehir, Turkey.
authors.forename: Gökhan
authors.initials: G
authors.lastname: Kuş
keywords: Breast cancer; Ceranib-2; Confocal; Ultrastructure