Apoptosis in cancer cells induced by photodynamic treatment - a methodological approach

Photodynamic therapy (PDT) is approved for clinical indications including several (pre-) cancers of the skin and solid tumors of the brain and the gastrointestinal tract. It operates by an acute cellular response caused by oxidation of cell components following light-induced and photosensitizer-mediated generation of reactive oxygen species. By this, PDT is capable of inducing the major types of cytotoxic responses: autophagy, apoptosis, and necrosis. As excited photosensitizer molecules react rather non-specifically with neighboring molecules, we suggest that with PDT and most (if not any) cell-localizing photosensitizers, all kinds of cellular responses can be provoked - following a strict dose-dependency, i.e. a transition from survival, over apoptosis to necrosis depending on the applied photosensitizer concentration or light dose. In this review, we briefly discuss (i) the types of cell death induced by PDT focusing on apoptosis induction, (ii) a simple experimental approach to quickly assess the dose-dependent phototoxic responses based on viability assays, and (iii) an overview of in vitro apoptosis detection methods for further in depth analyses. With this conceptual framework, we attempt to provide a rational experimental approach for initial in vitro, cell-based characterization of newly synthesized photosensitizers or formulations thereof - thus to plug the gap between subsequent in vivo evaluation and the preceding fundamental (physico-)chemical work devoted to the improvement of photosensitizing drugs based on mainly porphyrins, phthalocyanines and their derivatives.