Biochemical Journal

Research article

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

Ashley A. POWELL, Janna M. LaRUE, A. K. BATTA, Jesse D. MARTINEZ

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 12h in the human colon cancer cell line HCT116. The moderately hydrophobic bile acids hyoDCA, lagoDCA, norDCA, homoUDCA and isoUDCA induced growth arrest at 12h 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 14C-labelled and 3H-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.

  • cellular uptake
  • colon cancer
  • deoxycholic acid
  • signal transduction pathways
  • ursodeoxycholic acid

Footnotes

  • Abbreviations used: CDCA, chenodeoxycholic acid; DCA, deoxycholic acid; DMEM, Dulbecco's modified Eagle's medium; UDCA, ursodeoxycholic acid.