Riboflavin acetate induces apoptosis in squamous carcinoma cells after photodynamic therapy

Several research efforts have been focused on finding newer and more efficient photosensitizers for photodynamic therapy (PDT). Although, it was demonstrated that riboflavin is an efficient photosensitizer for PDT, the effect of its ester derivate, riboflavin 2′,3′,4′,5′-tetraacetate (RFTA), which h...

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Detalles Bibliográficos
Autores: Juarez, Andrea Virginia, Sosa, Liliana del Valle, de Paul, Ana Lucia, Costa, Ana Paula, Farina, Marcelo, Leal, Rodrigo B., Torres, Alicia Ines, Pons, Patricia
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2015
País:Argentina
Institución:Consejo Nacional de Investigaciones Científicas y Técnicas
Repositorio:CONICET Digital (CONICET)
Idioma:inglés
OAI Identifier:oai:ri.conicet.gov.ar:11336/50591
Acceso en línea:http://hdl.handle.net/11336/50591
Access Level:acceso abierto
Palabra clave:Photodynamic Therapy
Scc-13 Cells
Riboflavin 2′,3′,4′,5′-Tetraacetate
Apoptosis
https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
Descripción
Sumario:Several research efforts have been focused on finding newer and more efficient photosensitizers for photodynamic therapy (PDT). Although, it was demonstrated that riboflavin is an efficient photosensitizer for PDT, the effect of its ester derivate, riboflavin 2′,3′,4′,5′-tetraacetate (RFTA), which has higher cellular uptake, has not been well defined. To evaluate the cell death generated by applying RFTA as the photosensitizer in PDT in a human cancer cell line of squamous carcinoma (SCC-13), these cells were incubated with riboflavin and its ester derivate, RFTA followed by irradiation with different blue light doses. Cell viability was evaluated using neutral red uptake assay and cell death was evaluated using transmission electron microscopy, TUNEL assay and annexin V-PE/7AAD double staining. The expression of caspase-3, Bax, Bcl-2, ERK 1/2 and p38MAPK was evaluated by Western blotting and generation of intracellular ROS and changes in anion superoxide levels were analyzed using 2′,7′-dichlorofluorescein-diacetate and dihydroethidium dye, respectively. RFTA-PDT generated a decrease in cancer cell viability in a light dose–response. Treated SCC-13 cells exhibited chromatin condensation, formation of apoptotic bodies, increases in TUNEL-positive cells, phosphatidylserine externalization and decreased procaspase-3 and Bcl-2 protein expression and increment of ERK 1/2 phosphorylation. Moreover, trolox abolished the effect of PDT on cell viability linking the increase in intracellular ROS levels with the cell death observed, whereas that the pre-treatment with MEK inhibitor did not induce changes in SCC-13 cell survival. These findings demonstrate the effects of RFTA in triggering apoptosis induced by ROS (\O2−) production after visible light irradiation of squamous carcinoma cells.