title: Rhodiola crenulata inhibits Wnt/β-catenin signaling in glioblastoma.
abstract: 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.
  
  
  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.
authors.affiliation: Department of Surgery, Baystate Medical Center, Tufts University School of Medicine, Springfield, Massachusetts; Pioneer Valley Life Sciences Institute, Springfield, Massachusetts.
authors.forename: Maria Carmen
authors.initials: MC
authors.lastname: Mora
authors.affiliation: Pioneer Valley Life Sciences Institute, Springfield, Massachusetts; University of Massachusetts Amherst, Amherst, Massachusetts.
authors.forename: Lotfi M
authors.initials: LM
authors.lastname: Bassa
authors.affiliation: Department of Surgery, Baystate Medical Center, Tufts University School of Medicine, Springfield, Massachusetts; Pioneer Valley Life Sciences Institute, Springfield, Massachusetts; University of Massachusetts Amherst, Amherst, Massachusetts.
authors.forename: Kaitlyn E
authors.initials: KE
authors.lastname: Wong
authors.affiliation: Department of Pediatric Surgery, Baystate Children's Hospital, Tufts University School of Medicine, Springfield, Massachusetts.
authors.forename: Michael V
authors.initials: MV
authors.lastname: Tirabassi
authors.affiliation: Department of Surgery, Baystate Medical Center, Tufts University School of Medicine, Springfield, Massachusetts; Pioneer Valley Life Sciences Institute, Springfield, Massachusetts; University of Massachusetts Amherst, Amherst, Massachusetts.
authors.forename: Richard B
authors.initials: RB
authors.lastname: Arenas
authors.affiliation: Pioneer Valley Life Sciences Institute, Springfield, Massachusetts; University of Massachusetts Amherst, Amherst, Massachusetts; Department of Academic Affairs, Baystate Medical Center, Springfield, Massachusetts. Electronic address: Sallie.Schneider@baystatehealth.org.
authors.forename: Sallie S
authors.initials: SS
authors.lastname: Schneider
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism; D015153:Blotting, Western; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D005909:Glioblastoma / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use*; D018517:Plant Roots; D060888:Real-Time Polymerase Chain Reaction; D029771:Rhodiola; D016896:Treatment Outcome; D060449:Wnt Signaling Pathway / Q000187:drug effects*
chemical_list: D014408:Biomarkers, Tumor; D010936:Plant Extracts
keywords: Differentiation; GFAP; Glioblastoma; Rhodiola; Wnt; β-Catenin