Figure 5
Schematic hypothetical sketch of CSC-induced cell death: signalling and execution of CSC-induced cell death. The schematic sketch is divided into two parts: the left side shows intracellular signalling after administration of 50 μg/ml CSC and the right side the intracellular signalling after treatment with 100 μ/ml CSC. In all, 50 μg/ml induces apoptotic-like signalling in endothelial cells: CSC constituents enter the cells via unknown mechanisms and induce the formation of ROS (or are itself the source for ROS). CSC constituents (e.g., polycyclic aromatic hydrocarbon (PAH)) causes DNA damage and induces the activation of P53. The signal is then redirected from the P53 to the mitochondria and induces the depolarisation of mitochondrial membrane potential. This depolarisation could also be induced direct by ROS. CSC-induced mitochondrial depolarisation and rupture of the outer membrane induces the release of AIF, its translocation to the nucleus and the fragmentation of the DNA. In total, 100 μg/ml induces programmed necrosis signalling in endothelial cells: CSC constituents enter the cells via unknown mechanisms and induce the formation of ROS (or are itself the source for ROS). CSC constituents (e.g., PAH) causes DNA damage without the activation of P53. Depolarisation of mitochondrial membrane potential is induced either by DNA damage signalling without P53 contribution or direct by ROS. The next step in cell death signalling is the damage of lysosomes either induced via a signal from the mitochondria or via CSC-induced ROS formation. Damage of lysosomes induces the release of lipases and protease, which in turn induces plasma membrane rupture and the release of DNAses, finally leading to complete DNA degradation
