Enhancement of butyrate-induced differentiation of HT-29 human colon carcinoma cells by 1,25-dihyroxyvitamin D 3

Abstract

The individual and combined effects of sodium butyrate (NaB) and 1,25-dihydroxyvitamin D 3 (1,25-(OH) 2D 3) on inhibition of cell growth and initiation of enterocytic differentiation were investigated in established HT-29 human colonic adenocarcinoma cells. 1,25-(OH) 2D 3 alone caused some growth restriction but failed to induce differentiation of HT-29 carcinoma cells into a more benign enterocytic phenotype, as assessed by the appearance of mucin-producing colonocytes (goblet cells), increased alkaline phosphatase activity, and the generation of flat foci. NaB, in contrast, produced considerable biochemical and morphologic differentiation along the enterocyte maturation pathway. Combined exposure of HT-29 cells to both NaB and 1,25-(OH) 2D 3, however, significantly augmented the frequency of differentiated colonocytes, growth inhibition, extent of goblet cell maturation attained, and level of alkaline phosphatase activity over that seen with NaB alone. These data suggest that the in vitro “differentiation” response of human carcinoma cells is a complex process which, like normal cell maturation within the colonic crypts in vivo, is modulatable (both qualitatively and quantitatively) as a function of inducer composition.