Figure 5.

Proposed cell death mechanism induced on TK6 cells after treatment with DEHP and MEHP. Events presented in this pathway are a summary of general events involved in apoptosis. As demonstrated in this study the cell death mechanism induced by DEHP and MEHP includes mitochondrial membrane permeability, generation of ROS and activation of caspases 3 and 7 (shaded shapes). Segmented lines indicate apoptotic contributing events that were not measured in this study but are proposed for DEHP and MEHP based on our findings. The differences observed in mitochondrial permeability, ROS and caspase activation levels generated by MEHP and DEHP imply that different factors are influencing their cell death mechanism. Although not tested in this study phthalates have shown to stimulate Ca²⁺ entry in the cells and mitochondria which increases ROS production as well as significant crossover between the two principal apoptosis pathways suggesting the existence of positive feedback loops (Palleschi et al. 2009; Bissonnette et al. 2008). The difference between the ROS generated by MEHP and DEHP may be caused also by the release and/or activation of specific mitochondrial proteins such as Prx3, COX-2 and cytochrome c oxidase.