Deoxycholic and chenodeoxycholic bile acids induce apoptosis via oxidative stress in human colon adenocarcinoma cells.

摘要: The continuous exposure of the colonic epithelium to high concentrations bile acids may exert cytotoxic effects and has been related pathogenesis colon cancer. A better knowledge mechanisms by which induce toxicity is still required be useful for development new therapeutic strategies. We have studied effect deoxycholic acid (DCA) chenodeoxycholic (CDCA) treatments in BCS-TC2 human adenocarcinoma cells. Both promote cell death, being this higher CDCA. Apoptosis detected after 30 min–2 h treatment, as observed detachment, loss membrane asymmetry, internucleosomal DNA degradation, appearance mitochondrial transition permeability (MPT), caspase Bax activation. At longer treatment times, apoptosis followed vitro secondary necrosis due impaired activity ATP depletion. Bile acid-induced a result oxidative stress with increased ROS generation mainly activation plasma enzymes, such NAD(P)H oxidases and, lower extent, PLA2. These lead potential release pro-apoptotic factors cytosol, confirmed caspase-9 -3, but not caspase-8. This initial apoptotic steps cleavage Bcl-2, allowing formation additional pores that amplify signal.