Inhibitory effects of Dulcitol on rat C6 glioma by regulating autophagy pathway

Nat Prod Res. 2020 May;34(10):1437-1441. doi: 10.1080/14786419.2018.1512994. Epub 2018 Nov 16.

Abstract

In the study, we treated C6 rat glioma cells with 25 mg/ml Dulcitol for 24 h. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays were used to detect cellular growth. The measurements of the superoxide dismutase (SOD), malondialdehyde (MDA) and catalase (CAT) were used to assess oxidative stress level. Western was performed to detect the autophagy and apoptosis expression. The data showed that Dulcitol significantly decreased the cell viability, upregulated the Bax level in mitochondria and the Cytochrome C level in cytoplasm, and downregulated anti-apoptotic protein Bcl-xl. Moreover, it enhanced MDA level, reduced CAT and SOD activities, decreased LC3-II/LC3-I ratio, and increased P62 expression. However, rapamycin increased autophagy level and cell viability, and decreased ROS in Dulcitol treated C6 cells. Moreover, Dulcitol inhibited the glioma growth and enhanced survival in vivo. These results suggest that Dulcitol evidently increase cellular ROS levels and apoptosis in glioma cells, which can be significantly regulated by autophagy.

Keywords: Dulcitol; ROS; apoptosis; autopahgy; glioma cells.

MeSH terms

  • Animals
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Apoptosis / drug effects
  • Autophagy / drug effects*
  • Brain Neoplasms / drug therapy*
  • Brain Neoplasms / metabolism
  • Brain Neoplasms / pathology
  • Catalase / metabolism
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Galactitol / pharmacology*
  • Glioma / drug therapy*
  • Glioma / metabolism
  • Glioma / pathology
  • Male
  • Malondialdehyde / metabolism
  • Mitochondria / drug effects
  • Mitochondria / metabolism
  • Oxidation-Reduction
  • Oxidative Stress / drug effects
  • Rats, Sprague-Dawley
  • Reactive Oxygen Species / metabolism
  • Superoxide Dismutase / metabolism
  • bcl-2-Associated X Protein / metabolism
  • bcl-X Protein / metabolism

Substances

  • Antineoplastic Agents, Phytogenic
  • Bax protein, rat
  • Bcl2l1 protein, rat
  • Reactive Oxygen Species
  • bcl-2-Associated X Protein
  • bcl-X Protein
  • Galactitol
  • Malondialdehyde
  • Catalase
  • Superoxide Dismutase