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PANC-1 cells proliferative response to ionizing radiation is related to GSK-3β phosphorylation.
MedLine Citation:
PMID:  23194191     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
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.
Authors:
Nora A Mohamad; Graciela P Cricco; Claudia M Cocca; Elena S Rivera; Rosa M Bergoc; Gabriela A Martín
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Biochemistry and cell biology = Biochimie et biologie cellulaire     Volume:  90     ISSN:  1208-6002     ISO Abbreviation:  Biochem. Cell Biol.     Publication Date:  2012 Dec 
Date Detail:
Created Date:  2012-11-30     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8606068     Medline TA:  Biochem Cell Biol     Country:  Canada    
Other Details:
Languages:  eng     Pagination:  779-90     Citation Subset:  IM    
Affiliation:
a Laboratorio de Radioisótopos. Facultad de Farmacia y Bioquímica. Universidad de Buenos Aires. Junín 956, C1113AAB, Buenos Aires, Argentina.
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