title: PANC-1 cells proliferative response to ionizing radiation is related to GSK-3β phosphorylation.
abstract: 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.affiliation: Laboratorio de Radioisótopos, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junín 956, C1113AAB, Buenos Aires, Argentina.
authors.forename: Nora A
authors.initials: NA
authors.lastname: Mohamad
authors.forename: Graciela P
authors.initials: GP
authors.lastname: Cricco
authors.forename: Claudia M
authors.initials: CM
authors.lastname: Cocca
authors.forename: Elena S
authors.initials: ES
authors.lastname: Rivera
authors.forename: Rosa M
authors.initials: RM
authors.lastname: Bergoc
authors.forename: Gabriela A
authors.initials: GA
authors.lastname: Martín
mesh_terms: D000230:Adenocarcinoma; D017209:Apoptosis; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000528:radiation effects*; D005720:Gamma Rays; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D010190:Pancreatic Neoplasms; D010766:Phosphorylation
chemical_list: C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3