title: Timing the multiple cell death pathways initiated by Rose Bengal acetate photodynamic therapy.
abstract: Rose Bengal acetate photodynamic therapy (RBAc-PDT) induced multiple cell death pathways in HeLa cells through ROS and ER stress. Indeed, apoptosis was the first preferred mechanism of death, and it was triggered by at least four different pathways, whose independent temporal activation ensures cell killing when one or several of the pathways are inactivated. Apoptosis occurred as early as 1 h after PDT through activation of intrinsic pathways, followed by activation of extrinsic, caspase-12-dependent and caspase-independent pathways, and by autophagy. The onset of the different apoptotic pathways and autophagy, that in our system had a pro-death role, was timed by determining the levels of caspases 9, 8, 3 and 12; Bcl-2 family; Hsp70; LC3B; GRP78 and phospho-eIF2α proteins. Interestingly, inhibition of one pathway, that is, caspase-9 (Z-LEHD-FMK), caspase-8 (Z-IETD-FMK), pan-caspases (Z-VAD-FMK), autophagy (3-MA) and necrosis (Nec-1), did not impair the activation of the others, suggesting that the independent onset of the different apoptotic pathways and autophagy did not occur in a subordinated manner. Altogether, our data indicate RBAc as a powerful photosensitiser that induces a prolonged cytotoxicity and time-related cell death onset by signals originating from or converging on almost all intracellular organelles. The fact that cancer cells can die through different mechanisms is a relevant clue in the choice and design of anticancer PDT.
authors.affiliation: Department of Biological and Environmental Science and Technology (Di.S.Te.B.A.), University of Salento, Lecce 73100, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Panzarini
authors.forename: V
authors.initials: V
authors.lastname: Inguscio
authors.forename: L
authors.initials: L
authors.lastname: Dini
mesh_terms: D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism; D000091342:Endoplasmic Reticulum Chaperone BiP; D006367:HeLa Cells; D006801:Humans; D008954:Models, Biological; D018384:Oxidative Stress / Q000187:drug effects; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D012395:Rose Bengal / Q000031:analogs & derivatives* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013997:Time Factors
chemical_list: D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D017319:Photosensitizing Agents; D017382:Reactive Oxygen Species; C501991:Rose Bengal acetate; D012395:Rose Bengal