To understand hypericin PDT, the mechanistical steps of the damaging and dying process need to be revealed. Cellular damage can follow certain pathways until the cells are finally dead, which is very characteristic and can be assigned to concrete cell death mechanisms. The two most common programmed cell deaths are apoptosis and necrosis . Apoptosis can be triggered intrinsically via a mitochondrial pathway or by external stimuli . Depending on the pathway type, it undergoes a cascade of various protein or enzyme activations, including Bax, apoptotic protease, caspases or procaspase 8, that initiate the systematic progression of cellular degradation . Typical morphological features of apoptosis are cell and nucleus shrinkage, nuclear chromatin condensation, nucleus break up and membrane blebbing . Necrosis, however, is induced via caspases-independent pathways and shows a partly different morphological outcome, entailing bleb formation, cellular swelling, chromatin condensation and cellular lysis . Further cell death mechanisms are ferroptosis or paraptosis as well as several hybrid forms, which are all either morphologically or genetically distinguishable from one another . So far, hypericin PDT was tested on umbilical vein endothelial, HepG2 and A431 human epidermoid carcinoma cells, where apoptosis was observed to be the dominant cell death mechanism . Necrosis was demonstrated to be the type of cell death mechanism in human colon adenocarcinoma HT-29 cells (41), whereas paraptosis was identified to be the underlying cell death mechanism in OVCAR-5 cells . Glioma cell lines were (already) used as in vitro brain tumor models. Investigations upon hypericin PDT revealed either apoptosis or necrosis as the primary cell death mechanism . These studies were mainly performed with flow cytometry, biological assays or different microscopy techniques, like confocal, conventional, and total internal reflection fluorescence microscopy.