Linarin suppresses glioma through inhibition of NF-κB/p65 and up-regulating p53 expression in vitro and in vivo

Biomed Pharmacother. 2017 Nov;95:363-374. doi: 10.1016/j.biopha.2017.08.023. Epub 2017 Sep 12.


Glioma is the most common form of malignant brain cancer with high mortality rate in human. Therefore, finding effective therapeutic strategy and revealing the underlying molecular mechanism is necessary. Plant-extracted flavonoid glycosides have been suggested to be bioactive compounds with pleiotropic functions, such as anti-cancer, anti-inflammatory, antioxidant and effects. Our study was attempted to explore the anti-cancer role of linarin (acacetin-7-O-β-d-rutinoside) in glioma in vitro and in vivo. Nuclear factor kappa-B (NF-κB) activity is a common phenomenon in various cancers, resulting in abnormal cell proliferation, malignant transformation, or resistance to cell death. P53, an essential tumor suppressor, plays an important role in preventing tumor progression. Our data indicated that linarin suppressed glioma cell proliferation and migration by inducing apoptosis, which was through reducing cell cycle-related signals, including Survivin, p-Rb, and Cyclin D1, while promoting p21, Bax, Caspase-3 and poly (ADP-ribose) polymerase (PARP) activation. Also, we found that linarin-reduced cellular proliferation of glioma was dependent on p53 up-regulation and Nuclear factor kappa-B (NF-κB)/p65-down-regulation, thereby inhibiting glioma cell growth. We further conformed the inhibitory effect of linarin in vivo using xenograft tumor model. Linarin significantly triggered apoptosis as well as the tumor growth in animals, accompanied with p53 increase and p65 decrease. Our data illustrated that linarin could be used as a promising candidate against glioma progression.

Keywords: Glioma; Linarin; Proliferation and apoptosis; p53; p65.

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Brain Neoplasms / drug therapy*
  • Brain Neoplasms / metabolism*
  • Brain Neoplasms / pathology
  • Brain Neoplasms / ultrastructure
  • Caspase 3 / metabolism
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Glioma / drug therapy*
  • Glioma / metabolism*
  • Glioma / pathology
  • Glioma / ultrastructure
  • Glycosides / pharmacology
  • Glycosides / therapeutic use*
  • Humans
  • Male
  • Mice, Inbred BALB C
  • Mice, Nude
  • Signal Transduction / drug effects
  • Transcription Factor RelA / metabolism*
  • Tumor Stem Cell Assay
  • Tumor Suppressor Protein p53 / metabolism*
  • Up-Regulation* / drug effects


  • Glycosides
  • Transcription Factor RelA
  • Tumor Suppressor Protein p53
  • Caspase 3
  • linarin