IIBBA   05544
INSTITUTO DE INVESTIGACIONES BIOQUIMICAS DE BUENOS AIRES
Unidad Ejecutora - UE
artículos
Título:
The natural flavonoid silybin improves the response to Photodynamic Therapy of bladder cancer cells.
Autor/es:
GÁNDARA L. ,; SANDES E.; DI VENOSA G.,; PRACK MC CORMICK B. ; RODRIGUEZ L. ; MAMONE L, ; BATLLE A. ,; EIJÁN A.M. ; CASAS A.
Revista:
JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY B-BIOLOGY
Editorial:
ELSEVIER SCIENCE SA
Referencias:
Lugar: Amsterdam; Año: 2014 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.