Rhodiola crenulata inhibits Wnt/β-catenin signaling in glioblastoma.

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.