title: Pluronic-based micelle encapsulation potentiates myricetin-induced cytotoxicity in human glioblastoma cells.
abstract: As one of the natural herbal flavonoids, myricetin has attracted much research interest, mainly owing to its remarkable anticancer properties and negligible side effects. It holds great potential to be developed as an ideal anticancer drug through improving its bioavailability. This study was performed to investigate the effects of Pluronic-based micelle encapsulation on myricetin-induced cytotoxicity and the mechanisms underlying its anticancer properties in human glioblastoma cells. Cell viability was assessed using a methylthiazol tetrazolium assay and a real-time cell analyzer. Immunoblotting and quantitative reverse transcriptase polymerase chain reaction techniques were used for determining the expression levels of related molecules in protein and mRNA. The results indicated that myricetin-induced cytotoxicity was highly potentiated by the encapsulation of myricetin. Mitochondrial apoptotic pathway was demonstrated to be involved in myricetin-induced glioblastoma cell death. The epidermal growth factor receptor (EGFR)/PI3K/Akt pathway located in the plasma membrane and cytosol and the RAS-ERK pathway located in mitochondria served as upstream and downstream targets, respectively, in myricetin-induced apoptosis. MiR-21 inhibitors interrupted the expression of EGFR, p-Akt, and K-Ras in the same fashion as myricetin-loaded mixed micelles (MYR-MCs) and miR-21 expression were dose-dependently inhibited by MYR-MCs, indicating the interaction of miR-21 with MYR-MCs. This study provided evidence supportive of further development of MYR-MC formulation for preferentially targeting mitochondria of glioblastoma cells.
authors.affiliation: Department of Neurosurgery, TaiHe Hospital, Hubei University of Medicine, Shiyan.
authors.forename: Xiang-Jun
authors.initials: XJ
authors.lastname: Tang
authors.affiliation: Department of Neurosurgery, TaiHe Hospital, Hubei University of Medicine, Shiyan.
authors.forename: Kuan-Ming
authors.initials: KM
authors.lastname: Huang
authors.affiliation: Department of Neurosurgery, TaiHe Hospital, Hubei University of Medicine, Shiyan.
authors.forename: Hui
authors.initials: H
authors.lastname: Gui
authors.affiliation: Department of Pharmaceutics, Shanghai Eighth People's Hospital, Jiangsu University, Shanghai, People's Republic of China.
authors.forename: Jun-Jie
authors.initials: JJ
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, TaiHe Hospital, Hubei University of Medicine, Shiyan.
authors.forename: Jun-Ti
authors.initials: JT
authors.lastname: Lu
authors.affiliation: Department of Neurosurgery, TaiHe Hospital, Hubei University of Medicine, Shiyan; Department of Surgery, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Long-Jun
authors.initials: LJ
authors.lastname: Dai
authors.affiliation: Department of Neurosurgery, TaiHe Hospital, Hubei University of Medicine, Shiyan.
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Pharmaceutics, Shanghai Eighth People's Hospital, Jiangsu University, Shanghai, People's Republic of China.
authors.forename: Gang
authors.initials: G
authors.lastname: Wang
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D066246:ErbB Receptors / Q000378:metabolism; D005419:Flavonoids / Q000494:pharmacology / Q000627:therapeutic use*; D005909:Glioblastoma / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology*; D006801:Humans; D008823:Micelles; D035683:MicroRNAs / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D020442:Poloxamer / Q000737:chemistry*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D005419:Flavonoids; C524940:MIRN21 microRNA, human; D008823:Micelles; D035683:MicroRNAs; D020442:Poloxamer; C040015:myricetin; C512478:EGFR protein, human; D066246:ErbB Receptors; D051057:Proto-Oncogene Proteins c-akt
keywords: EGFR; anticancer; drug delivery; glioblastoma; miR-21; mitochondrial apoptosis; mixed micelles; myricetin