Cytotoxic and Apoptotic Impacts of Ceranib-2 on RAW 264.7 Macrophage Cells.

Abstract

Many ceramidase inhibitors have been developed and identified as potential treatment agents for various types of tumors in the last several decades. In recent years, their therapeutic potential against tumors has gained great attention. Inhibition of ceramidase is r eportedly related to apoptosis and cytotoxicity in macrophages, which are closely related to tumor development and progression. However, whether and how ceranib-2, a novel ceramidase inhibitor, can exert its cytotoxic and apoptotic effects on RAW 264.7, a macrophage cell line established from a tumor in a male mouse induced with the Abelson murine leukemia virus, remains unknown. In this study, we aimed to investigate whether and how ceranib-2 can exert cytotoxic, antiproliferative, and apoptotic effects on the RAW264.7 macrophages. We performed the MTT assay, Annexin V staining assay, and confocal microscopy to detect the cytotoxicity, apoptosis, and morphological changes, respectively, in the RAW264.7 cells. The viability of RAW264.7 cells treated with ceranib-2 was decreased as the doses of ceranib-2 increased at 24 h and 48 h due to apoptosis resulting from ceranib-2-reduced integrity of the mitochondrial membrane. Moreover, morphological changes were observed in these ceranib-2 exposed cells, further indicating the role of ceranib-2 in inducing apoptosis in these cells. Ceranib-2 is cytotoxic to RAW 264.7 macrophages and can induce apoptosis in these cells.