Diosmin Inhibits Glioblastoma Growth through Inhibition of Autophagic Flux

Int J Mol Sci. 2021 Sep 28;22(19):10453. doi: 10.3390/ijms221910453.

Abstract

Diosmin, a natural flavone glycoside acquired through dehydrogenation of the analogous flavanone glycoside hesperidin, is plentiful in many citrus fruits. Glioblastoma multiforme (GBM) is the most malignant primary brain tumor; the average survival time of GBM patients is less than 18 months after standard treatment. The present study demonstrated that diosmin, which is able to cross the blood-brain barrier, inhibited GBM cell growth in vitro and in vivo. Diosmin also impeded migration and invasion by GBM8401and LN229 GBM cells by suppressing epithelial-mesenchymal transition, as indicated by increased expression of E-cadherin and decreased expression of Snail and Twist. Diosmin also suppressed autophagic flux, as indicated by increased expression of LC3-II and p62, and induced cell cycle arrest at G1 phase. Importantly, diosmin did not exert serious cytotoxic effects toward control SVG-p12 astrocytes, though it did reduce astrocyte viability at high concentrations. These findings provide potentially helpful support to the development of new therapies for the treatment of GBM.

Keywords: autophagy; diosmin; glioblastoma multiforme.

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Autophagy / drug effects*
  • Brain Neoplasms / drug therapy*
  • Brain Neoplasms / physiopathology
  • Cell Line, Tumor
  • Diosmin / pharmacology*
  • Diosmin / therapeutic use
  • Epithelial-Mesenchymal Transition / drug effects*
  • Female
  • Glioblastoma / drug therapy*
  • Glioblastoma / physiopathology
  • Humans
  • Mice
  • Mice, Nude
  • Xenograft Model Antitumor Assays

Substances

  • Antineoplastic Agents
  • Diosmin