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.

Keywords:

• myricetin
• glioblastoma
• EGFR
• miR-21
• mitochondrial apoptosis
• mixed micelles
• anticancer
• drug delivery

Acknowledgments

This work was supported by Taihe Hospital Foundation and Young Talent Project of the Education Department of Hubei Province (Q20162104). We thank Dr Shan Qing Jiang for his technical assistance, Dr Feng-Qian Li for revising this paper, and Dr Jia-Lan Guo for analyzing the results. We also thank James Dai for his assistance in preparing the manuscript and English proofreading.

Disclosure

The authors report no conflicts of interest in this work.