INVESTIGADORES
COCCA Claudia Marcela
artículos
Título:
PANC-1 cells proliferative response to ionizing radiation is related to GSK-3β phosphorylation
Autor/es:
MOHAMAD N; CRICCO G; COCCA C; RIVERA E; BERGOC R; MARTÍN G
Revista:
BIOCHEMISTRY AND CELL BIOLOGY (ONLINE)
Editorial:
Canadian Science Publishing
Referencias:
Año: 2012 vol. 90 p. 779 - 790
ISSN:
1208-6002
Resumen:
Radiotherapy may be used to treat
pancreatic cancer and relieve pain. We have previously reported that
histamine modulates pancreatic adenocarcinoma PANC-1 cell proliferation.
This work was aimed to evaluate whether histamine improves
radiosensitivity of PANC-1 cells in relation to
phosphorylation/inhibition of glycogen synthase kinase-3β (GSK-3β).
Immediately after γ irradiation, intracellular hydrogen peroxide was
markedly decreased together with a rapid increase in catalase activity.
Although histamine diminished catalase activity in nonirradiated cells,
it only partially hindered the increase observed in irradiated cells and
could not modify radiosensitivity. In control cells, a high expression
of total and a very low expression of phosphorylated/inactive GSK-3β
were found. An increment in reactive oxygen species levels produced an
augmentation in GSK-3β phosphorylation and suppressed cell
proliferation. In both control and histamine-treated irradiated cells,
the rise in catalase activity lowered reactive oxygen species levels and
only a small increase in phosphorylated GSK-3β was detected.
Alternatively, 3-aminotriazole, an irreversible inhibitor of catalase,
reduced the survival fraction in irradiated control cells along with an
increment in phosphorylated GSK-3β. These results suggest that upon
irradiation, early catalase activation may be responsible for keeping
GSK-3β active conceding cells a survival advantage toward cytotoxic
effects of ionizing radiation.