Paraptosis after ER Photodamage Initiated by m-tetra(hydroxyphenyl) Chlorin

Two cell lines, A549 (human-derived nonsmall-cell lung cancer) and 1c1c7 (mouse hepatoma), were photosensitized with m-THPC and irradiated under LD₉₀ conditions. After 4 h, a pattern of cytoplasmic vacuoles had formed consistent with the initiation of paraptosis. After irradiation, there was no detectable loss of the mitochondrial membrane potential indicating no significant photodamage to mitochondria. We did, however, observe localization of m-THPC in the endoplasmic reticulum (ER), as indicated by fluorescence microscopy. Subsequent ER perturbation is known to result in initiation of paraptosis, another pathway to cell death. While an apoptotic response to m-THPC has been reported, the ability to target ER and induce paraptosis could explain the efficacy of this agent which could therefore eradicate cell types with an impaired apoptotic response.