Endogenous Ceramides (generated in response to bacterial sphingomyelinase overexpression or daunorubicin treatment) inhibits mRNA synthesis of telomerase reverse transcriptase and telomerase activity via inactivation of c-Myc transcription factor in the A549 human lung adenocarcinoma cell line.
The sustained generation of long chain endogenous ceramide requires the biochemical recycling of the sphingosine backbone of C6-ceramide, which involves deacylation and reacylation of ceramide for the generation of endogenous long chain ceramide (mainly C16:0- and C24:1-Ceramides), most likely by CoA-dependent ceramide synthase, which is inhibited by fumonisin B1. In A549 cells the generation of long chain endogenous ceramide mediates the effects of exogenous C6-ceramide on growth inhibition, cell cycle arrest, and the modulation of telomerase activity.