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

A. A. Powell, J. M. LaRue, A. K. Batta, J. D. Martinez

Research output: Contribution to journalArticle

100 Scopus citations

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 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 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.

Original languageEnglish (US)
Pages (from-to)481-486
Number of pages6
JournalBiochemical Journal
Volume356
Issue number2
DOIs
StatePublished - Jun 1 2001

Keywords

  • Cellular uptake
  • Colon cancer
  • Deoxycholic acid
  • Signal transduction pathways
  • Ursodeoxycholic acid

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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