β-Hydroxyisovalerylshikonin induces apoptosis and G0/G1 cell-cycle arrest of endometriotic stromal cells: A preliminary in vitro study

Abstract

Background: Most of the current medical treatments for endometriosis aim to down-regulate the estrogen activity. However, a high recurrence rate after medical treatments has been the most significant problem. β-Hydroxyisovalerylshikonin (β-HIVS) is an ATP non-competitive inhibitor of protein-tyrosine kinases and is considered an apoptosis-inducing agent. The aim of this study is to evaluate the effects of β-HIVS on the proliferation, cell cycle and apoptosis of endometriotic stromal cells. Methods: We investigated the effects of β-HIVS on cultured ovarian endometriotic cyst stromal cells (ECSC) by a modified methylthiazoletetrazolium (MTT) assay, a 5-bromo-2′-deoxyuridine (BrdU) incorporation assay and internucleosomal DNA fragmentation assays. The effect of β-HIVS on the cell cycle of ECSC was determined by flow cytometry. The expression of apoptosis-related molecules was examined in ECSC using western blot analysis. Results: β-HIVS significantly inhibited the proliferation and DNA synthesis of ECSC and induced apoptosis and G0/G1 phase cell-cycle arrest of these cells. Down-regulation of the B-cell lymphoma/ leukaemia-2 (Bcl-2) expression with the activation of caspase-3, caspase-8 and caspase-9 was observed in ECSC after β-HIVS treatment. Conclusions: These results suggest that β-HIVS induces apoptosis of ECSC by suppressing anti-apoptotic proteins. Although our present findings are preliminary, β-HIVS could potentially be a therapeutic agent for the treatment of endometriosis. © 2006 Oxford University Press.