INDUCTION OF GALECTIN-1 EXPRESSION IN HUMAN COLON-CARCINOMA CELLS BY HISTONE DEACETYLASE INHIBITORS

(R)-trichostatin A {(R)-TSA; N-hydroxy-4,6-dimethyl-7-oxo-2,4-heptadie n-amide}, a potent histone deacetylase inhibitor, was found to suppres s cell proliferation, suppress the transformed phenotype, and enhance the differentiation of various malignant cells, including the KM12 hum an colon carcinoma cells. We found that KM12 cells treated with (R)-TS A for 3 h exhibited a high degree of histone H4 acetylation. (R)-TSA i nduced the expression of galectin-1, a 14.5-kDa galactoside-binding pr otein, at concentrations in the range between 0.1 to 1 mu M that are a t least 1000 times lower than those required to achieve similar effect s by n-butyrate, another histone deacetylase inhibitor, which we have shown previously to induce galectin-1 in the KM12 cells. The effect of (R)-TSA was observed at both the mRNA and protein levels as early as 6 h after treatment. Trichostatin C, which exhibits some histone deace tylase inhibitory activity, but not the analogs (S)-TSA or (R)- or (S) -trichostatic acid, which lack histone deacetylase inhibitory activity , also showed some induction of galectin-1. (R)-TSA enhanced the trans activation of galectin-1 promoter-reporter constructs. These results i ndicate that the effect of (R)-TSA on galectin-1 expression was, at le ast in part, at the level of transcription.