CIPYP   05508
CENTRO DE INVESTIGACIONES SOBRE PORFIRINAS Y PORFIRIAS
Unidad Ejecutora - UE
artículos
Título:
The natural flavonoid silybin improves the response to Photodynamic Therapy of bladder cancer cells.
Autor/es:
GANDARA, LAUTARO; SANDES, EDUARDO; DI VENOSA, GABRIELA; PRACK MC CORMICK, B; RODRÍGUEZ, LORENA; MAMONE, LEANDRO; BATLLE, ALCIRA; EIJÁN, ANA MARIA; CASAS, ADIRANA
Revista:
JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY B-BIOLOGY
Editorial:
ELSEVIER SCIENCE SA
Referencias:
Lugar: Amsterdam; Año: 2014 vol. 133 p. 55 - 64
ISSN:
1011-1344
Resumen:
Photodynamic Therapy (PDT) is an anticancer
treatment based on photosensitisation of malignant cells. The precursor
of the photosensitiser Protoporphyrin IX, 5-aminolevulinic acid (ALA),
has been used for PDT of bladder cancer. Silybin is a flavonoid
extracted from Silybum marianum, and it has been reported to increase
the efficacy of several anticancer treatments. In the present work, we
evaluated the cytotoxicity of the combination of ALA-PDT and silybin in
the T24 and MB49 bladder cancer cell lines. MB49 cells were more
sensitive to PDT damage, which was correlated with a higher
Protoporphyrin IX production from ALA. Employing lethal light doses 50%
(LD50) and 75% (LD75) and additional silybin treatment, there was a
further increase of toxicity driven by PDT in both cell lines. Using the
Chou-Talalay model for drug combination derived from the mass-action
law principle, it was possible to identify the effect of the combination
as synergic when using LD75, whilst the use of LD50 led to an additive
effect on MB49 cells. On the other hand, the drug combination turned out
to be nearly additive on T24 cells. Apoptotic cell death is involved
both in silybin and PDT cytotoxicity in the MB49 line but there is no
apparent correlation with the additive or synergic effect observed on
cell viability. On the other hand, we found an enhancement of the
PDT-driven impairment of cell migration on both cell lines as a
consequence of silybin treatment. Overall, our results suggest that the
combination of silybin and ALA-PDT would increase PDT outcome, leading
to additive or synergistic effects and possibly impairing the occurrence
of metastases.