Ceramide. a product of sphingomyelin hydrolysis, has been proposed as a lipid second messenger ymediating antiproliferative activation. In this study, we examined the role of the cell cycle-related proteins in the ceramide-mediated growth suppression....
Ceramide. a product of sphingomyelin hydrolysis, has been proposed as a lipid second messenger ymediating antiproliferative activation. In this study, we examined the role of the cell cycle-related proteins in the ceramide-mediated growth suppression. Treatment of U-937 cells with C2-ceramide(N-acetylsphingosine) resulted in growth suppression in a time- and concentration dependent manner. Ceramide induced concentration dependent dephosphorylation of retinoblastoma gene product (Rb). Rb remains hypophosphorylated in synchronized cells even after serum stimulation in the presence of ceramide. Ceramide decreased the expression of cyclin D1 and cyclin E levels. These results suggest that antiproliferative effect of ceramide is associated with hypophosphorylation of Rb and decreased expression of cyclin D1 and cyclin E.