FOXO3a-mediated suppression of the self-renewal capacity of sphere-forming cells derived from the ovarian cancer SKOV3 cell line by 7-difluoromethoxy1-5,4′-di-n-octyl genistein

Carcinogenesis is predominantly dependent on the cancer stem cells (CSCs) residing or populating within the cancer. We previously demonstrated that the novel synthetic genistein analogue, 7-difluoromethoxy1-5,4'-di-n-octylgenistein (DFOG), induced apoptotic cell death of ovarian and gastric cancer cells. The present study demonstrated that sphere-forming cells (SFCs) derived from the ovarian cancer cell-line SKOV3 possessed ovarian cancer stem-like cell (OCSLC) properties, including self-renewal and high tumorigenicity. DFOG may be effective in inhibiting the self-renewal capacity of SFCs derived from the SKOV3 cell line. DFOG decreased the level of phosphorylated FOXO3a protein in SKOV3 cell-derived SFCs. The inhibition of FOXO3a expression by siRNA significantly attenuated the ability of DFOG to inhibit the self-renewal capacity of SKOV3-derived SFCs. Our results suggested that DFOG has been demonstrated to significantly inhibit the self-renewal capacity of ovarian cancer stem cells (OCSCs) through a mechanism partly dependent on the activation of FOXO3a.