Photodynamic therapy and paraptosis: an update

Two death pathways have been associated with photodynamic therapy (PDT): apoptosis and paraptosis. The former is characterized by caspase activation and nuclear fragmentation while the latter is associated with an unfolded protein response leading to an extensive pattern of cytoplasmic vacuole formation. In this study, we explore some of the determinants of a response involving paraptosis after photodynamic therapy in cell culture using a human-derived ovarian cancer cell line: OVCAR-5 cells. Experimental results are consistent with the hypothesis that paraptosis is evoked by ER photodamage. This leads to an extensive pattern of cytoplasmic vacuolization. While activation of JNK and related MAP kinases has been associated with paraptosis, the JNK antagonist SP600125 did not prevent a paraptotic response to ER photodamage in OVCAR-5. Translocation of the nuclear HMGB1 to the cell periphery had been proposed as a potential marker for paraptosis. We found this effect was not a reliable marker for paraptosis. Targeting the ER for photodamage may, however, be a useful approach to eradicating malignant cells with an impaired route to apoptosis.