Histone deacetylase inhibitors trichostatin A and valproic acid induce cell cycle arrest and p21 expression in immortalized human endometrial stromal cells

OBJECTIVE: Following our observation that histone deacetylase inhibitors (HDACIs) trichostatin A (TSA) and valproic acid (VPA) can suppress proliferation of endometrial stromal cells, we sought to determine whether TSA and VPA do so by inducing cell cycle arrest and p21 expression. STUDY DESIGN: A recently established immortalized endometrial stromal cell line was treated with TSA, VPA, and/or all-trans retinoic acid (ATRA) and the consequent cell cycle progression was measured by flow cytometry and p21 protein expression by Western blot analysis. RESULTS: Both TSA and VPA induced cell cycle arrest and p21 expression in a concentration-dependent manner. Treatment with ATRA alone also induced cell cycle arrest and moderate increase in p21 expression but joint treatment of ATRA and TSA/VPA did not further enhance cell cycle arrest as compared with TSA/VPA treatment alone. CONCLUSIONS: HDACIs suppress proliferation of endometrial stromal cells through induction of cell cycle arrest and possibly also through apoptosis as well. RA also induces cell cycle arrest but it does not synergize with HDACIs in inducing cell cycle arrest. HDACIs may be promising compounds for treating endometriosis.