CONICET | Buscador de Institutos y Recursos Humanos

Radiotherapy may be used to treat non-spread pancreatic cancer and also to relieve pain. We have previously reported that histamine modulates human pancreatic adenocarcinoma PANC-1 cells proliferation. This work was aimed to evaluate if histamine may improve radiosensitivity of PANC-1 cells in relation to phosphorylation/inhibition of glycogen synthase kinase-3beta (GSK-3beta ). When cells were gamma irradiated survival curves showed that histamine could not modify radiosensibility. Immediately after irradiation, intracellular hydrogen peroxide was markedly decreased in a way associated to a rapid increase in catalase activity. Although histamine diminished catalase activity in non irradiated cells, it was able to partially hinder the increase observed in irradiated cells. In control cells a high expression of total GSK-3beta together with a very low expression of phosphorylated/inactive GSK-3beta was found. An increment in intracellular reactive oxygen species levels produced an augmentation in GSK-3beta phosphorylation and suppressed cell proliferation. In irradiated control cells the rise in catalase activity lowered reactive oxygen species levels and only a small increase in phosphorylated GSK-3beta was detected. Similar results were observed in histamine treated irradiated cells. Alternatively 3-aminotriazole, an irreversible inhibitor of catalase activity, significantly reduced survival fraction in irradiated control cells along with an increment in phosphorylated GSK-3beta levels. These results suggest that upon irradiation, early catalase activation may be responsible for keeping GSK-3beta active endowing cells with a survival advantage toward cytotoxic effects of ionizing radiation.

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