3-Hydroxy-3′,4′-dimethoxyflavone suppresses Bcl-w-induced invasive potentials and stemness in glioblastoma multiforme

• Published in: Biochemical and biophysical research communications Vol. 450; no. 1; pp. 704 - 710
• Main Authors: Bae, In Hwa, Lee, Woo Sang, Yun, Dong Ho, Han, Young-Hoon, Lee, Jae-Seon
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 18.07.2014
• Subjects: Antineoplastic Agents - administration & dosage; Apoptosis - drug effects; Apoptosis Regulatory Proteins - metabolism; Cell Line, Tumor; Cell Movement - drug effects; Cell Survival - drug effects; Dose-Response Relationship, Drug; Flavones - administration & dosage; GBM; Glioblastoma - drug therapy; Glioblastoma - pathology; Glioblastoma - physiopathology; HDMF; Humans; Invasion; Migration; MMP-3; Neoplasm Invasiveness; Neoplastic Stem Cells - drug effects; Neoplastic Stem Cells - pathology; Neoplastic Stem Cells - physiology; Stemness; Treatment Outcome; Stemness; GBM; HDMF; Bcl-w; Migration; MMP-3; MMP-9; Invasion
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2014.06.038

•HDMF had significantly decreased Bcl-w-induced migration and invasion.•HDMF inhibited Bcl-w-induced stemness in U251 or U87MG cells.•HDMF functioned as a negative agent for inhibiting aggressiveness of glioma cells. 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).