title: Apigenin Inhibits Cancer Stem Cell-Like Phenotypes in Human Glioblastoma Cells via Suppression of c-Met Signaling.
abstract: Glioblastoma (GBM) is a highly malignant human brain tumor with limited treatment choices. The extremely aggressive characteristics of GBM result from GBM stem cells (GSCs), a subpopulation in tumor having self-renewal potential and resistance to chemotherapy and radiotherapy. Therefore, eliminating GSCs is an effective strategy to treat this fatal disease. In this study, we investigated the therapeutic effects of dietary flavonoids, including apigenin, quercetin, and naringenin, against cancer stem cell-like phenotypes of human GBM cell lines U87MG and U373MG. Among flavonoids studied, apigenin and quercetin significantly suppressed not only the self-renewal capacity such as cell growth and clonogenicity, but also the invasiveness of GBM stem-like cells. Notably, apigenin blocked the phosphorylation of c-Met and its downstream effectors, transducer and activator of transcription 3, AKT (Protein kinase B), and mitogen-activated protein kinase in the GSCs, thereby reducing the expression levels of GSC markers such as CD133, Nanog, and Sox2. These results suggest that the GSC inhibition effect of apigenin may be caused by downregulation of c-Met signaling pathway.
authors.affiliation: Department of BT-Convergent Pharmaceutical Engineering, Sun Moon University, 70, Sunmoon-ro 221, Tangjeong-myeon, Asan-si, Chungnam, 336-708, Korea.
authors.forename: Boram
authors.initials: B
authors.lastname: Kim
authors.affiliation: Department of BT-Convergent Pharmaceutical Engineering, Sun Moon University, 70, Sunmoon-ro 221, Tangjeong-myeon, Asan-si, Chungnam, 336-708, Korea.
authors.forename: Narae
authors.initials: N
authors.lastname: Jung
authors.affiliation: Department of BT-Convergent Pharmaceutical Engineering, Sun Moon University, 70, Sunmoon-ro 221, Tangjeong-myeon, Asan-si, Chungnam, 336-708, Korea.
authors.forename: Sanghun
authors.initials: S
authors.lastname: Lee
authors.affiliation: Department of BT-Convergent Pharmaceutical Engineering, Sun Moon University, 70, Sunmoon-ro 221, Tangjeong-myeon, Asan-si, Chungnam, 336-708, Korea.
authors.forename: Jae Kyung
authors.initials: JK
authors.lastname: Sohng
authors.affiliation: Department of BT-Convergent Pharmaceutical Engineering, Sun Moon University, 70, Sunmoon-ro 221, Tangjeong-myeon, Asan-si, Chungnam, 336-708, Korea. poka96@sunmoon.ac.kr.
authors.forename: Hye Jin
authors.initials: HJ
authors.lastname: Jung
mesh_terms: D047310:Apigenin / Q000737:chemistry* / Q000494:pharmacology; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005909:Glioblastoma / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D014411:Neoplastic Stem Cells / Q000187:drug effects*; D010641:Phenotype; D019859:Proto-Oncogene Proteins c-met / Q000737:chemistry*; D015398:Signal Transduction
chemical_list: D047310:Apigenin; C491743:MET protein, human; D019859:Proto-Oncogene Proteins c-met
keywords: apigenin; c-Met; cancer stem cell; flavonoid; glioblastoma