Figure 6
From: p53-mediated delayed NF-κB activity enhances etoposide-induced cell death in medulloblastoma
Molecular mechanisms of etoposide-induced cell death in brain tumours. The schematic diagram represents a model of intracellular mechanism induced by etoposide in both GM and MB cells. Depending on the genetic background, cells display different sensitivity to etoposide. Through its genotoxic function, etoposide induces p53 activation. p53 activates the transcription of various genes involved in regulation of cell cycle arrest and cell death as Fas receptor and mdm2. Fas receptor expression at the plasma membrane is able to activate p65 in a FasL-independent manner as well as a caspase-dependent apoptotic cell death. p65 enhances apoptotic death by inducing a caspase-independent cell death. Cells displaying this fully efficient crosstalk are very sensitive to etoposide-induced cell death (D283-MED, D458-MED). Conversely, cells impaired in p53 activation are strongly resistant to cell death (MEB-Med8A, D566-MG, T98G). Interestingly, Cells displaying p53 activity but an impaired p65 activation show intermediate resistance (MHH-Med1, U87MG). MB cell lines are in blue and GM cell lines in green. The grey-to-black gradient illustrates the sensitivity to etoposide-induced cell death. The dotted red lines represent the nods in transduction pathways that are blocked in indicated cell lines
