Abstract
Photodynamic therapy (PDT) is a cancer treatment modality based on the administration of a photosensitizer (PS), which accumulates preferentially in tumor cells. Subsequent irradiation of the neoplastic area triggers a cascade of photochemical reactions that leads to the formation of highly reactive oxygen species responsible for cell inactivation. Photodynamic treatments in vitro are performed with the PS, zinc-phthalocyanine (ZnPc). The PS is near the plasma membrane during uptake and internalization. Inactivation clearly occurs by a necrotic process, manifested by nuclear pyknosis, negative TUNEL and Annexin V assays and non-relocation of cytochrome c. In contrast, by increasing the incubation time, ZnPc is accumulated in the Golgi apparatus and produces cell inactivation with characteristics of apoptosis and necrosis: TUNEL positive, relocated cytochrome c and negative Annexin V assay. This type of death produces a still undescribed granulated nuclear morphology, which is different from that of necrosis or apoptosis. This morphology is inhibited by necrostatin-1, a specific inhibitor of regulated necrosis.
Highlights
Photodynamic therapy (PDT) is a cancer treatment modality based on the administration of a photosensitizer (PS) that accumulates preferentially in tumor cells [1,2,3]
The results indicate that when the PS is observed in the Golgi apparatus (GA), the irradiation triggers a process of regulated necrosis, leading to a specific nuclear morphology different from that described for apoptosis or necrosis
Taking into account the localization of the PS, we evaluated the effect of photodynamic treatment on the GA by immunofluorescence of golgin-130 (GM130)
Summary
Photodynamic therapy (PDT) is a cancer treatment modality based on the administration (systemic or topical) of a photosensitizer (PS) that accumulates preferentially in tumor cells [1,2,3]. Photodynamic treatments induce different mechanisms of cell death, such as apoptosis, necrosis, autophagy or mitotic catastrophe [8,9,10]. Recent studies suggest that PDT with 5-aminolevulinic acid (5-ALA) is able to induce regulated necrosis in glioblastoma and osteosarcoma cells. In this case, the inductor stimulus is 1O2 originated in the mitochondria that provokes the formation of a receptor-interacting protein 3 (RIP-3). The results indicate that when the PS is observed in the Golgi apparatus (GA), the irradiation triggers a process of regulated necrosis, leading to a specific nuclear morphology different from that described for apoptosis or necrosis. On the contrary, when ZnPc is located in the plasma membrane [13], due to the internalization process, photodynamic treatments induce necrotic cell death
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