Bile acid hydrophobicity is correlated with induction of apoptosis and/or growth arrest in HCT116 cells
- 1 June 2001
- journal article
- Published by Portland Press Ltd. in Biochemical Journal
- Vol. 356 (2), 481-6
- https://doi.org/10.1042/0264-6021:3560481
Abstract
Faecal bile acids have long been associated with colon cancer; highly hydrophobic bile acids, which induce apoptosis, have been implicated in the promotion of colon tumours. The moderately hydrophobic chemopreventive agent ursodeoxycholic acid (UDCA) does not induce apoptosis; rather, it causes colon-derived tumour cells to arrest their growth. To investigate the relationship between bile acid hydrophobicity and biological activity we examined 26 bile acids for their capacity to induce apoptosis or alter cell growth. We found that the rapidity with which, and the degree to which, bile acids could induce apoptosis or growth arrest was correlated with their relative hydrophobicities. Of the bile acids tested, only deoxycholic acid (DCA) and chenodeoxycholic acid, the most hydrophobic bile acids tested, could induce apoptosis in less than 12 h in the human colon cancer cell line HCT116. The moderately hydrophobic bile acids hyoDCA, lagoDCA, norDCA, homoUDCA and isoUDCA induced growth arrest at 12 h but longer incubations resulted in apoptosis. Conjugation of glycine or taurine to the bile acids decreased relative hydrophobicity and eliminated biological activity in our assays. In addition, we tested a subset of these bile acids for their ability to translocate across cell membranes. When (14)C-labelled and (3)H-labelled DCA, UDCA and lagoDCA were added to cell cultures, we found only minimal uptake by colon cells, whereas hepatocytes had considerably higher absorption. These experiments suggest that hydrophobicity is an important determinant of the biological activity exhibited by bile acids but that under our conditions these activities are not correlated with cellular uptake.This publication has 22 references indexed in Scilit:
- Role of bile metabolites in colon carcinogenesis. Animal modelsCancer, 2006
- Characterization of bile salt-induced apoptosis in colon cancer cell lines.2000
- Bile salts mediate hepatocyte apoptosis by increasing cell surface trafficking of FasAmerican Journal of Physiology-Gastrointestinal and Liver Physiology, 2000
- Bile Acid-induced Activation of Activator Protein-1 Requires Both Extracellular Signal-regulated Kinase and Protein Kinase C SignalingOnline Journal of Public Health Informatics, 2000
- Effect of tauroursodeoxycholic acid on bile acid‐induced apoptosis in primary human hepatocytesEuropean Journal of Clinical Investigation, 2000
- Bile Acids: Natural Ligands for an Orphan Nuclear ReceptorScience, 1999
- Toxic bile salts induce rodent hepatocyte apoptosis via direct activation of FasJCI Insight, 1999
- The chemopreventive role of ursodeoxycholic acid in azoxymethane-treated rats: suppressive effects on enhanced group II phospholipase A2 expression in colonic tissueCancer Letters, 1998
- Effects of different bile salts upon the composition and morphology of a liver plasma membrane preparation. Deoxycholate is more membrane damaging than cholate and its conjugatesBiochimica et Biophysica Acta (BBA) - Biomembranes, 1977
- Degradation of bile salts by human intestinal bacteria.Gut, 1969