By generating reactive oxygen species (ROS), MS-275, a histone deacetylase inhibitor, can selectively induce transforming growth factor beta type II receptor expression in human breast cancer cells. MS-275 showed antiproliferative activity against all human breast cancer cell lines examined and induced TbetaRII mRNA, but not TGF-beta type I receptor mRNA. MS-275 caused an accumulation of acetylated histones H3 and H4 in total cellular chromatin. At a low concentration of 1 uM, MS-275 exhibits potent antiproliferative activity, inducing p21(CIP1/WAF1)-mediated growth arrest and expression of differentiation markers (CD11b) in U937 cells, by increasing in reactive oxygen species (ROS).