7-difluoromethoxyl-5,4'-di-n-octyl genistein inhibits ovarian cancer stem cell characteristics through the downregulation of FOXM1

摘要

7-Difluoromethoxyl-5,4'-di-n-octylgenistein (DFOG) is a novel synthetic genistein analogue that possesses anti-cancer activity in a variety of cancers, including ovarian cancer. The objective of the present study was to investigate whether DFOG inhibits the self-renewal capacity of ovarian cancer stem-like cells (OCSLCs) and to identify its potential mechanism of action. It was found that the sphere-forming cells (SFCs) of the SKOV3 cell line exhibited a self-renewal capacity and high tumorigenicity, indicating that they possessed the properties of ovarian cancer stem cells (OCSCs). It was also shown for the first time that DFOG preferentially inhibited proliferation, self-renewal capacity and expression of stem cell markers [cluster of differentiation (CD)133, CD44 and aldehyde dehydrogenase 1 (ALDH1)] in the SFCs derived from the SKOV3 cells. These effects were accompanied by the downregulation of forkhead box M1 (FOXM1) expression. Overexpression of FOXM1 rescued the DFOG-induced downregulation of FOXM1, CD133, CD44 and ALDH1 protein expression. It also inhibited the self-renewal capacity of the SFCs derived from the SKOV3 cells. Thus, DFOG appears to inhibit the characteristics of OCSLCs by downregulating FOXM1 expression.