Effect of histone deacetylase inhibitors on angiogenic, invasive and adhesive factors in endometriosis

Despite of several therapeutic options in the treatment of endometriosis, most of them are symptomatically oriented. Histone deacetylase-inhibitors (HDACi) are a novel class of epigenetic acting drugs that inhibit growth and induce apoptosis in cancer cells. HDACi have been shown to cause hyperacetylation of histones, and thus, to effect the reactivation of silenced genes. HDACi have furthermore the advantage of being less toxic in normal cells than in cancer cells. Endometriosis, although known as benign disorder, shares some characteristics with cancers such as cell adhesion, degradation of the extracellular matrix and angiogenesis. The study aimed at investigating whether HDACi are able to modulate the expression of adhesive, invasive and angiogenic proteins in an endometriotic cell line. We treated an immortalized, human epithelial endometriotic cell line with the HDAC-Inhibitors SAHA and Romidepsin at various concentrations and durations and examined the effect on cell viability by MTT-assays. Protein and mRNA levels were measured by western blot analyses and RT-PCR. The effect of SAHA and Romidepsin treatment could be demonstrated by the acetylation of histones, activation of the cell-cycle-inhibitor p21 and PARP–1 cleavage. The amount of cell adhesion molecules (cadherin) and VEGF declined, as well as the expression of MMP–2 and MMP–9 and some phosphorylated proteins of the MEK-ERK-STAT3 signal transduction. This makes the class of HDACi very promising in the development of a new treatment of an existing endometriosis or recurrence prophylaxis.