Sodium butyrate increases the effect of the photodynamic therapy: a mechanism that involves modulation of gene expression and differentiation in astrocytoma cells.
OBJECTIVE
In order to evaluate the improvement of the photodynamic therapy (PDT) due to sodium butyrate (NaBu), its effectiveness in U373-MG and D54-MG astrocytoma cell lines was evaluated.


METHODS
Cells were exposed to delta-aminolevulinic acid (δ-ALA) as a precursor to endogenous photosensitizer protoporphyrin IX (PpIX). In both astrocytoma cells, an important increase by ALA was observed in uroporphyrinogen synthetase gene expression: 1.8- and 52-fold for D54-MG and U373-MG cells, respectively. After irradiation, they showed 16.67 and 28.9% of mortality in U373-MG and D54-MG, respectively. These mortalities increased to 70.62 and 96.7% when U373-MG and D54-MG cells, respectively, were exposed 24 h to 8 mM NaBu, before to PpIX induction. NaBu induced expression of caspase-3, caspase-9, and Bcl-2 and increased Bax in U373-MG cells. ALA-induced morphological changes are compatible to differentiation.


CONCLUSIONS
Genes and differentiation induced mainly by NaBu improve cell death performed by PDT in astrocytoma cells. These facts prove the synergistic effect of NaBu on cytotoxic damage induced by PDT.
Instituto Tecnológico de Sonora, Avenida Antonio Caso s/n Colonia Villa ITSON, 85120, Sonora, Mexico.
José
J
Bueno-Carrazco
Violeta
V
Castro-Leyva
Fanny
F
García-Gomez
Mario
M
Solís-Paredes
Eva
E
Ramon-Gallegos
Alfredo
A
Cruz-Orea
Pilar
P
Eguía-Aguilar
Francisco
F
Arenas-Huertero
D001254:Astrocytoma / Q000378:metabolism / Q000473:pathology; D002087:Butyrates / Q000494:pharmacology*; D020169:Caspases / Q000235:genetics / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects*; D045744:Cell Line, Tumor; D003720:Densitometry; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006801:Humans; D017319:Photosensitizing Agents / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D011524:Protoporphyrins / Q000494:pharmacology*; D050998:bcl-2 Homologous Antagonist-Killer Protein / Q000235:genetics / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism
C494772:BAK1 protein, human; D002087:Butyrates; D005904:Glial Fibrillary Acidic Protein; D017319:Photosensitizing Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D011524:Protoporphyrins; D050998:bcl-2 Homologous Antagonist-Killer Protein; D051028:bcl-2-Associated X Protein; C028025:protoporphyrin IX; D020169:Caspases