title: FOXO3a-mediated suppression of the self-renewal capacity of sphere-forming cells derived from the ovarian cancer SKOV3 cell line by 7-difluoromethoxyl-5,4'-di-n-octyl genistein.
abstract: 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-difluoromethoxyl-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.
authors.affiliation: Department of Gynaecology and Obstetrics, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, P.R. China.
authors.forename: Yingxia
authors.initials: Y
authors.lastname: Ning
authors.affiliation: Department of Oncological Surgery, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou 510150, P.R. China.
authors.forename: Chaoyuan
authors.initials: C
authors.lastname: Luo
authors.affiliation: Laboratory of Medicine Engineering, Medical College, Hunan Normal University, Changsha, Hunan 410013, P.R. China.
authors.forename: Kaiqun
authors.initials: K
authors.lastname: Ren
authors.affiliation: Laboratory of Medicine Engineering, Medical College, Hunan Normal University, Changsha, Hunan 410013, P.R. China.
authors.forename: Meifang
authors.initials: M
authors.lastname: Quan
authors.affiliation: Laboratory of Medicine Engineering, Medical College, Hunan Normal University, Changsha, Hunan 410013, P.R. China.
authors.forename: Jianguo
authors.initials: J
authors.lastname: Cao
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors / Q000235:genetics* / Q000378:metabolism; D055786:Gene Knockout Techniques; D019833:Genistein / Q000031:analogs & derivatives* / Q000494:pharmacology; D064593:Heterografts; D006801:Humans; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000378:metabolism*; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000473:pathology; D010766:Phosphorylation / Q000187:drug effects; D018874:Spheroids, Cellular; D014407:Tumor Cells, Cultured; D014410:Tumor Stem Cell Assay
chemical_list: C579741:7-difluoromethoxyl-5,4'-di-n-octylgenistein; D014408:Biomarkers, Tumor; C499517:FOXO3 protein, human; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors; D019833:Genistein