Potentiation of glucocorticoid-mediated gene expression by the novel benzoquinone derivative (2E)-3-[5-(2,3-dimethoxy-o-methyl-1,4-benzoquinoyl)]-2-nonyl-2-propenoic acid (E3330)

Abstract

We examined the effects of the novel benzoquinone derivative (2E-3-[5-(2,3-dimethoxy-o-methyl-1,4-benzoquinoyl)]-2-nonyl-2- propenoic acid, E3330, on the functional activity of the glucocorticoid receptors. For that purpose we used a cloned CHOpMTGR cells, in which human glucocorticoid receptor cDNA was stably transfected and glucocorticoid receptor was expressed at high levels. After treatment of CHOpMTGR cells with E3330, neither the ligand binding activity nor immunoreactivity of the glucocorticoid receptor was affected. Moreover, E3330 did not affect the sequence-specific DNA binding activity of partially-purified glucocorticoid receptor in vitro. However, a glucocorticoid-inducible promoter was activated by E3330 in a dose-dependent fashion in the presence of the synthetic ligand dexamethasone. Interestingly, E3330 increased nuclear translocation of the glucocorticoid receptor in a ligand-independent fashion, indicating that E3330, through facilitation of the translocation of the glucocorticoid receptor, augments glucocorticoid-mediated gene transcription.