Ferroptosis as a predominant pathway in photodynamic therapy of primary human gliomas: harnessing cyanoarylporphyrazine for regulated and potentially immunogenic cell death

ABSTRACT: Background: Photodynamic therapy (PDT) leading to immunogenic cell death (ICD) may serve as a promising basis for the development of antitumor therapeutic strategies. However, the mechanisms of action of photoinduced ICD in primary tumor cultures, including human glioma, remain unexplored. Methods: In the present study, the features of regulated cell death induced by photodynamic therapy using a previously described ICD inducer, porphyrazine III (pz III), were investigated. Cell death was studied in 7 primary cultures of high-grade human gliomas (astrocytomas, oligodendrogliomas, and glioblastomas). Results: Accumulation of porphyrazine III was shown in the endoplasmic reticulum (ER), Golgi apparatus, lysosomes, and mitochondria; however, the distribution of the photosensitizer varied across different cultures. A narrow concentration window of pz III was achieved to effectively reach IC85, primarily inducing ferroptosis accompanied by superoxide anion generation and mitochondrial dysfunction. Conclusions: Given the immunogenic potential of ferroptosis, we hypothesize that the induction of PDT using porphyrazine III in glioma will trigger immunogenic cell death.

SUBMITTER: Ekaterina Sleptsova 

PROVIDER: S-BIAD3271 | bioimages |

REPOSITORIES: bioimages