Effects of ceranib-2 on cell survival and TNF-alpha in colon cancer cell line

Abstract

OBJECTIVE: The aim of this study was to investigate the effects of a novel anti-cancer drug, ceranib-2, which targets the acid ceramidase, in human colon cancer cell line. MATERIALS AND METHODS: The cell lines were treated with 50 μM of ceranib-2. Relative mRNA expression of TNF-alpha, TNF-R1 and ASAH were assessed by quantitative RT-PCR. RESULTS: Ceranib-2 reduced cell viability in a dose-dependent manner and the apoptotic values of cells following treatment with the dose of 50 μM were reduced significantly both at 24 h and 48 h compared to the control cells (p < 0.001). TNF-alpha receptor 1 (TNF-R1) mRNA levels were reduced significantly in the cell lines treated with both 25 μM and 50 μM of ceranib-2 for 24 h compared to the control cells (p < 0.05), whereas the difference between the treatment and the control cell lines diminished at 48 h. The human acid ceramidase gene (ASAH) mRNA levels were significantly higher in the cell lines treated with 50 μM of ceranib-2 for 48 h than in the other cell lines (p < 0.001). CONCLUSION: The study shows that ceranib-2 increased apoptosis by inducing ASAH expression and reduced TNF-R1 expression in human colon cancer cell lines in a dose and time-dependent manner.