TAUROURSODEOXYCHOLIC ACID PROTECTS IN-VITRO MODELS OF HUMAN COLONIC-CANCER CELLS FROM CYTOTOXIC EFFECTS OF HYDROPHOBIC BILE-ACIDS

Bile acids have been implicated as tumor promoters that enhance epithe lial proliferation and the development of colonic tumors. This study i nvestigated the effects of bile acids on the growth of in vitro models of human colonic epithelial cells. Cell lines with varying degrees of differentiation (Caco2, HT29, LS174T, and Love) were studied. Cell vi ability and number were measured by a tetrazolium (MTT) spectrophotome tric assay. Enhanced cell growth was not observed with any bile acid o ver the range 10 nmol/L to 2.5 mmol/L. Cytotoxicity was consistently o bserved at concentrations of unconjugated bile acids greater than 0.1 mmol/L. The bile acid concentration at which 50% growth inhibition occ urred was similar for all cell lines and increased in the following or der: deoxycholic acid = chenodeoxycholic acid < taurodeoxycholic acid < ursodeoxycholic acid < taurochenodeoxycholic acid < cholic acid < ta uroursodeoxycholic acid. Coincubation of tauroursodeoxycholic acid (TU DC) with taurodeoxycholic acid (TDC) or taurochenodeoxycholic acid (TD CD) reversed the short-term (30-minute) cytotoxicity and release of gl ycoprotein induced by TDC or TCDC regardless of differentiation status . In contrast, TUDC did not reverse the cytotoxicity of deoxycholic ac id. Unconjugated ursodeoxycholic acid did not alter short-term cytotox icity of any bile acid. These data indicate that bile acids do not sti mulate cell growth in undifferentiated or differentiated colon cancer cell lines, in contrast to normal colonic epithelium in vivo. Bile aci d cytotoxicity correlates with the relative hydrophobicity of the bile acid. Because tauroursodeoxycholic acid alters the cytotoxicity of hy drophobic bile acids in vitro, further understanding of bile acid inte ractions in the colon may have important implications in altering tumo r promotion.