Photodynamic therapy with redaporfin targets the endoplasmic reticulum and Golgi apparatus.
Preclinical evidence depicts the capacity of redaporfin (Redp) to act as potent photosensitizer, causing direct antineoplastic effects as well as indirect immune-dependent destruction of malignant lesions. Here, we investigated the mechanisms through which photodynamic therapy (PDT) with redaporfin kills cancer cells. Subcellular localization and fractionation studies based on the physicochemical properties of redaporfin revealed its selective tropism for the endoplasmic reticulum (ER) and the Golgi apparatus (GA). When activated, redaporfin caused rapid reactive oxygen species-dependent perturbation of ER/GA compartments, coupled to ER stress and an inhibition of the GA-dependent secretory pathway. This led to a general inhibition of protein secretion by PDT-treated cancer cells. The ER/GA play a role upstream of mitochondria in the lethal signaling pathway triggered by redaporfin-based PDT Pharmacological perturbation of GA function or homeostasis reduces mitochondrial permeabilization. In contrast, removal of the pro-apoptotic multidomain proteins BAX and BAK or pretreatment with protease inhibitors reduced cell killing, yet left the GA perturbation unaffected. Altogether, these results point to the capacity of redaporfin to kill tumor cells via destroying ER/GA function.
['Gomes-da-Silva|Lígia C|LC|', 'Zhao|Liwei|L|', 'Bezu|Lucillia|L|', 'Zhou|Heng|H|', 'Sauvat|Allan|A|', 'Liu|Peng|P|0000-0002-1682-9222', 'Durand|Sylvère|S|', 'Leduc|Marion|M|', 'Souquere|Sylvie|S|', 'Loos|Friedemann|F|0000-0002-5976-5978', 'Mondragón|Laura|L|', 'Sveinbjørnsson|Baldur|B|', 'Rekdal|Øystein|Ø|', 'Boncompain|Gaelle|G|', 'Perez|Franck|F|0000-0002-9129-9401', 'Arnaut|Luis G|LG|', 'Kepp|Oliver|O|0000-0002-6081-9558', 'Kroemer|Guido|G|0000-0002-9334-4405']
D000818:Animals D017209:Apoptosis D045744:Cell Line, Tumor D004721:Endoplasmic Reticulum D005260:Female D006056:Golgi Apparatus D006801:Humans D008027:Light D008810:Mice, Inbred C57BL D010778:Photochemotherapy D017319:Photosensitizing Agents D011166:Porphyrins D013449:Sulfonamides
photodynamic therapy redaporfin Golgi apparatus Golgi‐targeting agents retrograde transport