Rhodiola crenulata inhibits Wnt/β-catenin signaling in glioblastoma

J Surg Res. 2015 Aug;197(2):247-55. doi: 10.1016/j.jss.2015.02.074. Epub 2015 Apr 23.


Background: Rhodiola crenulata is a perennial plant that grows in the high altitudes of Eastern Europe and Asia. R crenulata has been used for many years in Eastern traditional medicine for a variety of medicinal purposes and it has been shown to elicit antineoplastic effects. The purpose of this study is to determine if R crenulata extract exhibits antitumor properties on glioblastoma multiforme (GBM), the most common and aggressive primary brain tumor.

Materials and methods: Human U87 GBM cells were treated with 200 μg/mL of R crenulata or vehicle control. Cell proliferation was measured via MTS assay and clonogenic assay. The expressions of glial fibrillary acidic protein, a protein marker of differentiation, E-cadherin, and non-phospho active β-catenin were measured with immunocytochemistry. Neurosphere assay was performed in low attachment plates. Activity of the Wnt/β-catenin transcriptional activation was assessed via a dual-luciferase assay.

Results: MTS and clonogenicity assays revealed a decrease in proliferation with R crenulata therapy with an increased sensitivity to radiation. Immunocytochemistry revealed that R crenulata induced glial fibrillary acidic protein and E-cadherin expression suggestive of a more differentiated state. In agreement with the change in differentiation neurosphere formation was decreased upon treatment with R crenulata. β-Catenin dual reporter assay revealed a decrease in Wnt promoter activity after treatment with R crenulata; this was supported by a decrease in nuclear localization of β-catenin.

Conclusions: Treatment with R crenulata extract effectively suppresses proliferation, stimulates differentiation, and eliminates tumorsphere formation of GBM cells in vitro. The observed effects are associated with inhibition of Wnt/β-catenin signaling pathway.

Keywords: Differentiation; GFAP; Glioblastoma; Rhodiola; Wnt; β-Catenin.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor / metabolism
  • Blotting, Western
  • Brain Neoplasms / drug therapy*
  • Brain Neoplasms / metabolism
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Glioblastoma / drug therapy*
  • Glioblastoma / metabolism
  • Humans
  • Immunohistochemistry
  • Phytotherapy*
  • Plant Extracts / pharmacology
  • Plant Extracts / therapeutic use*
  • Plant Roots
  • Real-Time Polymerase Chain Reaction
  • Rhodiola*
  • Treatment Outcome
  • Wnt Signaling Pathway / drug effects*


  • Biomarkers, Tumor
  • Plant Extracts