EFFECTS OF CHOLATE AND DEOXICHOLATE SODIUM SALTS ON MCF-7 CELL LINE

GANDOLA Y.; FONTANA C.; LUSCHNAT T.; MORETTON M.A.; CHIAPPETTA D.A.; VERSTRAETEN S.; GONZALEZ L.

Encuentro; REUNIÓN CONJUNTA DE SOCIEDADES DE BIOCIENCIAS; 2017

Biliary acids (BA) are bioactive molecules with multiple metabolic actions and pharmaceutical applications. High levels of BA were associated with colon, stomach, pancreas and also breast tissue tumorogenesis. Considering BA association with cancer pathology and their use in pharmaceutical technology, it is highly relevant to study their biological effects. The objective of this work was to analyse the molecular and cellular effects of sodium cholate (SC) and deoxycholate (SDC) on the epithelial breast cancer cells MCF-7. For this purpose, effects over cell proliferation, migration, membrane fluidity and activation of signaling molecules, involved in cell cycle and survival promotion, were studied. Moreover, SC and SDC preparations used for in vitro assays were characterized by electron microscopy and dynamic light scattering. MCF-7 cells were incubated with different concentrations of each bile salt for 48 hours and cell proliferation was assessed by BrdU incorporation. Results showed that SC 10 uM and SDC 5 uM induced an increase in cell proliferation. Assessment of Akt and Erk1/2 phosphorylation and Cyclin D1 expression at different time points by Immunoblotting evidenced that SC 10 uM and SDC 5 uM induced a slight activation of Akt and an increased in Cyclin D1 protein levels. Wound healing assay showed no significant effects on cell migration for those BS concentrations. PA-DPH fluorescence anisotropy revealed that low concentrations of SC and SDC had no effect on membrane fluidity during the first hour and after 24 hours treatment with the biliary salts. Morphological characterization of BS preparations revealed particles in the nanoscale. In conclusion, biliary salts have pro-proliferative effects over the MCF-7 cell line while no significant action over cell migration was observed. BS cellular effects might be consequence of specific receptor activation/modulation as unspecific effects of the nanostructures over membrane fluidity were not observed.