Liposomal temocene (m-THPPo) photodynamic treatment induces cell death by mitochondria-independent apoptosis

Jorge Soriano, María García-Díaz, Margarita Mora, Maria Lluïsa Sagristá, Santi Nonell, Angeles Villanueva, Juan Carlos Stockert, Magdalena Cañete

Producció científica: Article en revista indexadaArticleAvaluat per experts

17 Cites (Scopus)

Resum

Background The cell death pathway activated after photodynamic therapy (PDT) is controlled by a variety of parameters including the chemical structure of the photosensitizer, its subcellular localization, and the photodynamic damage induced. The present study aims to characterize a suitable m-THPPo liposomal formulation, to determine its subcellular localization in HeLa cells and to establish the cell death mechanisms that are activated after photodynamic treatments. Methods Liposomes containing m-THPPo were prepared from a mixture of DPPC and DMPG at a 9:1 molar ratio. In order to procure the best encapsulation efficiency, the m-THPPo/lipid molar ratio was considered. HeLa cells were incubated with liposomal m-THPPo and the subcellular localization of m-THPPo was studied. Several assays such as TUNEL, annexin V/propidium iodide and Hoechst-33258 staining were performed after photodynamic treatments. The apoptotic initiation was assessed by cytochrome c and caspase-2 immunofluorescence. Results m-THPPo encapsulated in liposomes showed a decrease of the fluorescence and singlet oxygen quantum yields, compared to those of m-THPPo dissolved in tetrahydrofuran. Liposomal m-THPPo showed colocalization with LysoTracker® and it induced photoinactivation of HeLa cells by an apoptotic mechanism. In apoptotic cells no relocalization of cytochrome c could be detected, but caspase-2 was positive immediately after photosensitizing treatments. Conclusions Photodynamic treatment with liposomal m-THPPo leads to a significant percentage of apoptotic morphology of HeLa cells. The activation of caspase-2, without the relocalization of cytochrome c, indicates a mitochondrial-independent apoptotic mechanism. General significance These results provide a better understanding of the cell death mechanism induced after liposomal m-THPPo photodynamic treatment.

Idioma originalAnglès
Pàgines (de-a)4611-4620
Nombre de pàgines10
RevistaBiochimica et Biophysica Acta - General Subjects
Volum1830
Número10
DOIs
Estat de la publicacióPublicada - 2013

Fingerprint

Navegar pels temes de recerca de 'Liposomal temocene (m-THPPo) photodynamic treatment induces cell death by mitochondria-independent apoptosis'. Junts formen un fingerprint únic.

Com citar-ho