Bile acid hydrophobicity is correlated with induction of apoptosis and/or growth arrest in HCT116 cells

Faecal bile acids have long been associated with colon cancer; highly hydro phobic bile acids, which induce apoptosis, have been implicated in the prom otion of colon tumours. The moderately hydrophobic chemopreventive agent ur sodeoxycholic acid (UDCA) does not induce apoptosis; rather, it causes colo n-derived tumour cells to arrest their growth. To investigate the relations hip 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 co uld induce apoptosis or growth arrest was correlated with their relative hy drophobicities. Of the bile acids tested, only deoxycholic acid (DCA) and c henodeoxycholic 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 is oUDCA induced growth arrest at 12 h but longer incubations resulted in apop tosis. Conjugation of glycine or taurine to the bile acids decreased relati ve hydrophobicity and eliminated biological activity in our assays. In addi tion, we tested a subset of these bile acids for their ability to transloca te across cell membranes. When C-14-labelled and H-3-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 exper iments suggest that hydrophobicity is an important determinant of the biolo gical activity exhibited by bile acids but that under our conditions these activities are not correlated with cellular uptake.