Comparison of a ceramidase inhibitor (ceranib-2) with C2 ceramide and cisplatin on cytotoxicity and apoptosis of glioma cells

Authors : Gökhan KUŞ, Mete ÖZKURT, Pınar ÖZTOPCU VATAN, Ruhi UYAR, Selda KABADERE

Pages : 259-265

View : 19 | Download : 9

Publication Date : 2018-12-01

Article Type : Research Paper

Abstract :  Inhibiting ceramidase activity in cancer cells has been identified as a promising target for cancer therapy in recent studies. Thus, we examined the possible role of ceranib-2, a novel ceramidase inhibitor, on growth and apoptotic mechanisms of the human normal glia cell line insert ignore into journalissuearticles values(HNA);, human glioma cell lines insert ignore into journalissuearticles values(T-98G and U-87MG);, and a rat glioma cell line insert ignore into journalissuearticles values(C6);. We also compared the results with the effects of C2 ceramide and cisplatin. We determined the in vitro survival rate with MTT assay, apoptosis with flow cytometry, gene expressions with qRT-PCR, and statistical significance by one-way analysis of variance together with Tukey`s test. Calculated from MTT outcomes, the inhibitory ranking was as follows: T-98G > U-87MG > C6 > HNA. Ceranib-2 had the most growth-suppressive activity on human T-98G cells with an IC50 of 7 μM for 24 h and 0.9 μM for 48 h. Only the 25 μM dose of ceranib-2 induced apoptosis of human T-98G and U-87MG cells after 24 h of treatment; however, it increased apoptosis of C6 cells dose- and time-dependently. Ceranib-2 increased the cytochrome c gene expression level during 24 h in T-98G cells. Ceranib-2 had cytotoxic and apoptotic effects on glioma cells but the cytotoxic effect was weaker on normal glia cells. This cytotoxicity was stronger than that of C2 ceramide and cisplatin.
Keywords : Ceranib 2, C2 ceramide, cisplatin, apoptosis, glioma