CONICET | Buscador de Institutos y Recursos Humanos

Biliary acids (BA) are bioactive molecules, mainly implicatedin fat diet absorption and digestion, which have multiple metab olicactions. Salts derived from BA are used for the design of severalpharmaceuticalnanoparticulated systems. However, high levelsof BA have been associated with tumorogenesis of the colon,oesophagus, stomach, pancreas and breast tissue. Consideringthe multiple biological actions of BA, their association with cancerpathology and their use in pharmaceutical technology, it is highlyrelevant to study their biological and toxic effects over cancer cells.The objective of this work was to analyze the molecular and cel lulareffects ofsodium cholate and deoxycholate salts (SC and SDC)over the epithelial breast cancer cells MCF-7. For this purpose, theeffects of bile salts over cell proliferation and apoptosis, and theactivation of signaling molecules involved in cell cycle and survivalpromotion were studied. MCF-7 cells were incubated with differentconcenviability wasassed by a colorimetric assay. Results showed thatboth biliary salts induced an increase in cell viability at low doses,but citotoxic effects were evidenced when cells were incubatedwith high SC and SDC concentrations. Cleavage of PARP, whichis a hallmark of apoptosis, was found to increase 24hours afterincubation with the highest SC concentration tested. Kinetic assaysof Akt and Erk1/2 phosphorylation evidenced that citotoxicconcentrations of SC and SDC induced a strong and sustainedactivation of both signalling mediators, while low SC and SDC concentrations only promoted a slight activation of Akt. In conclusion,biliary salts have a dosage-dependent effect over the MCF-7 cellsviability. Citotoxicity induced by high bile salts concentrations couldbe associated to the marked and sustained activation of signallingmediators involved in cell proliferation and survival.trations of each bile salt during 24 and 48 hours and cell