Recommended Conferences

Cancer-Treatment and Therapeutics

New York, USA
Related Subjects
 

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

Author(s): Ignacio BJ, Olmo N, Perez-Ramos P, Santiago-Gómez A, Lecona E, Turnay J, et al

Abstract

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

Similar Articles

Gut microbiota role in dietary protein metabolism and health-related outcomes: The two sides of the coin

Author(s): Portune KJ, Beaumont M, Davila AM, Tomé D, Blachier F, Sanz Y

Intestinal bile acid physiology and pathophysiology

Author(s): Martínez-Augustin O, Sánchez de Medina F

Dose-dependent antiinflammatory effect of ursodeoxycholic acid in experimental colitis

Author(s): Martínez-Moya P, Romero-Calvo I, Requena P, Hernández-Chirlaque C, Aranda CJ, González R, et al

Effect of ursodeoxycholic acid on bile acid profiles and intestinal detoxification machinery in primary biliary cirrhosis and health

Author(s): Dilger K, Hohenester S, Winkler-Budenhofer U, Bastiaansen BAJ, Schaap FG, Rust C, et al

Bile acids as carcinogens in human gastrointestinal cancers

Author(s): Bernstein H, Bernstein C, Payne CM, Dvorakova K, Garewal H

Bile acids regulate intestinal cell proliferation by modulating EGFR and FXR signaling

Author(s): Dossa AY, Escobar O, Golden J, Frey MR, Ford HF, Gayer CP

A regulatory cascade of the nuclear receptors FXR, SHP-1, and LRH-1 represses bile acid biosynthesis

Author(s): Goodwin B, Jones SA, Price RR, Watson MA, McKee DD, Moore LB, et al

Effects of chenodeoxycholate and a bile acid sequestrant, colesevelam, on intestinal transit and bowel function

Author(s): Odunsi-Shiyanbade ST, Camilleri M, McKinzie S, Burton D, Carlson P, Busciglio IP, et al

Increase in fecal primary bile acids and dysbiosis in patients with diarrhea-predominant irritable bowel syndrome

Author(s): Duboc H, Rainteau D, Rajca S, Humbert L, Farabos D, Maubert M, et al

Connecting dysbiosis, bile-acid dysmetabolism and gut inflammation in inflammatory bowel diseases

Author(s): Duboc H, Rajca S, Rainteau D, Benarous D, Maubert MA, Quervain E, et al