4.7 Article

Diosmin Inhibits Glioblastoma Growth through Inhibition of Autophagic Flux

Journal

Publisher

MDPI
DOI: 10.3390/ijms221910453

Keywords

diosmin; glioblastoma multiforme; autophagy

Funding

  1. Tri-Service General Hospital [TSGH-E-109227, TSGH-E-110195]
  2. Ministry of National Defense Medical Affairs Bureau [MAB-108-064]
  3. Ministry of Science and Technology [MOST 108-2314-B-016-024, MOST-110-2314-B-016-035]

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Diosmin, a natural flavone glycoside, demonstrated inhibitory effects on GBM cell growth, migration, and invasion, as well as modulation of autophagy and cell cycle progression. It showed limited cytotoxicity towards astrocytes and holds potential for new GBM treatment therapies.
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.

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