title: 3-Hydroxy-3',4'-dimethoxyflavone suppresses Bcl-w-induced invasive potentials and stemness in glioblastoma multiforme.
abstract: 3-Hydroxy-3',4'-dimethoxyflavone (HDMF) is a natural chemical product that is not currently regarded as a drug. In our study, we employed glioblastoma cells and cell biology and biochemistry approaches to investigate the potential of HDMF as a natural anticancer therapy option. FACS analysis showed that treatment concentration of HDMF does not exert cytotoxicity on U251 cells. Wound-healing and invasion assays showed that HDMF dose-dependently decreased the migratory and invasive potentials of these cells, likely by indirectly inhibiting MMP-3 activity as a result of the inhibition of p38 and ERK signaling proteins - an effect of HDMF also shown by Western blotting. HDMF inhibits Bcl-w-induced neurosphere formation and the expression of glioma stem cell markers, such as Musashi, Sox-2 and c-myc. These results indicate that HDMF suppresses migratory or invasive potentials and stemness and functions as a negative agent against the aggressiveness of glioblastoma cells. We propose that HDMF has potential as anticancer drug for inhibiting the aggressiveness of glioblastoma multiforme (GBM).
authors.affiliation: Division of Radiation Cancer Research, Korea Institute of Radiological & Medical Sciences, Seoul, Republic of Korea. Electronic address: ihbae@kirams.re.kr.
authors.forename: In Hwa
authors.initials: IH
authors.lastname: Bae
authors.affiliation: Division of Radiation Cancer Research, Korea Institute of Radiological & Medical Sciences, Seoul, Republic of Korea.
authors.forename: Woo Sang
authors.initials: WS
authors.lastname: Lee
authors.affiliation: Division of Radiation Cancer Research, Korea Institute of Radiological & Medical Sciences, Seoul, Republic of Korea.
authors.forename: Dong Ho
authors.initials: DH
authors.lastname: Yun
authors.affiliation: Division of Radiation Cancer Research, Korea Institute of Radiological & Medical Sciences, Seoul, Republic of Korea.
authors.forename: Young-Hoon
authors.initials: YH
authors.lastname: Han
authors.affiliation: Department of Biomedical Sciences, College of Medicine, Inha University, Incheon, Republic of Korea.
authors.forename: Jae-Seon
authors.initials: JS
authors.lastname: Lee
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage; D017209:Apoptosis / Q000187:drug effects; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D047309:Flavones / Q000008:administration & dosage*; D005909:Glioblastoma / Q000188:drug therapy / Q000473:pathology* / Q000503:physiopathology*; D006801:Humans; D009361:Neoplasm Invasiveness; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000473:pathology* / Q000502:physiology*; D016896:Treatment Outcome
chemical_list: C509288:3',4'-dimethoxyflavone; D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; C491073:BCL2L2 protein, human; D047309:Flavones
keywords: GBM; HDMF; Invasion; MMP-3; Migration; Stemness