Pluronic-based micelle encapsulation potentiates myricetin-induced cytotoxicity in human glioblastoma cells

Xiang-Jun Tang,1,* Kuan-Ming Huang,1,* Hui Gui,1,* Jun-Jie Wang,2 Jun-Ti Lu,1 Long-Jun Dai,1,3 Li Zhang,1 Gang Wang2 1Department of Neurosurgery, TaiHe Hospital, Hubei University of Medicine, Shiyan, 2Department of Pharmaceutics, Shanghai Eighth People’s Hospital, Jiangsu University, Shan...

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Autores principales:	Tang XJ, Huang KM, Gui H, Wang JJ, Lu JT, Dai LJ, Zhang L, Wang G
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2016
Materias:	Myricetin glioblastoma EGFR miR-21 mitochondrial apoptosis mixed micelles Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/0e55860e3f1a452987344088d7634464
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spelling	oai:doaj.org-article:0e55860e3f1a452987344088d76344642021-12-02T02:31:38ZPluronic-based micelle encapsulation potentiates myricetin-induced cytotoxicity in human glioblastoma cells1178-2013https://doaj.org/article/0e55860e3f1a452987344088d76344642016-10-01T00:00:00Zhttps://www.dovepress.com/pluronic-based-micelle-encapsulation-potentiates-myricetin-induced-cyt-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Xiang-Jun Tang,1,* Kuan-Ming Huang,1,* Hui Gui,1,* Jun-Jie Wang,2 Jun-Ti Lu,1 Long-Jun Dai,1,3 Li Zhang,1 Gang Wang2 1Department of Neurosurgery, TaiHe Hospital, Hubei University of Medicine, Shiyan, 2Department of Pharmaceutics, Shanghai Eighth People’s Hospital, Jiangsu University, Shanghai, People’s Republic of China; 3Department of Surgery, University of British Columbia, Vancouver, BC, Canada *These authors contributed equally to this work 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. Keywords: myricetin, glioblastoma, EGFR, miR-21, mitochondrial apoptosis, mixed micelles, anticancer, drug deliveryTang XJHuang KMGui HWang JJLu JTDai LJZhang LWang GDove Medical PressarticleMyricetinglioblastomaEGFRmiR-21mitochondrial apoptosismixed micellesMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 11, Pp 4991-5002 (2016)
institution	DOAJ
collection	DOAJ
language	EN
topic	Myricetin glioblastoma EGFR miR-21 mitochondrial apoptosis mixed micelles Medicine (General) R5-920
spellingShingle	Myricetin glioblastoma EGFR miR-21 mitochondrial apoptosis mixed micelles Medicine (General) R5-920 Tang XJ Huang KM Gui H Wang JJ Lu JT Dai LJ Zhang L Wang G Pluronic-based micelle encapsulation potentiates myricetin-induced cytotoxicity in human glioblastoma cells
description	Xiang-Jun Tang,1,* Kuan-Ming Huang,1,* Hui Gui,1,* Jun-Jie Wang,2 Jun-Ti Lu,1 Long-Jun Dai,1,3 Li Zhang,1 Gang Wang2 1Department of Neurosurgery, TaiHe Hospital, Hubei University of Medicine, Shiyan, 2Department of Pharmaceutics, Shanghai Eighth People’s Hospital, Jiangsu University, Shanghai, People’s Republic of China; 3Department of Surgery, University of British Columbia, Vancouver, BC, Canada *These authors contributed equally to this work 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. Keywords: myricetin, glioblastoma, EGFR, miR-21, mitochondrial apoptosis, mixed micelles, anticancer, drug delivery
format	article
author	Tang XJ Huang KM Gui H Wang JJ Lu JT Dai LJ Zhang L Wang G
author_facet	Tang XJ Huang KM Gui H Wang JJ Lu JT Dai LJ Zhang L Wang G
author_sort	Tang XJ
title	Pluronic-based micelle encapsulation potentiates myricetin-induced cytotoxicity in human glioblastoma cells
title_short	Pluronic-based micelle encapsulation potentiates myricetin-induced cytotoxicity in human glioblastoma cells
title_full	Pluronic-based micelle encapsulation potentiates myricetin-induced cytotoxicity in human glioblastoma cells
title_fullStr	Pluronic-based micelle encapsulation potentiates myricetin-induced cytotoxicity in human glioblastoma cells
title_full_unstemmed	Pluronic-based micelle encapsulation potentiates myricetin-induced cytotoxicity in human glioblastoma cells
title_sort	pluronic-based micelle encapsulation potentiates myricetin-induced cytotoxicity in human glioblastoma cells
publisher	Dove Medical Press
publishDate	2016
url	https://doaj.org/article/0e55860e3f1a452987344088d7634464
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_version_	1718402390210641920

Pluronic-based micelle encapsulation potentiates myricetin-induced cytotoxicity in human glioblastoma cells

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