Resveratrol Impairs Glioma Stem Cells Proliferation and Motility by Modulating the Wnt Signaling Pathway

Abstract

Glioblastoma multiforme (GBM) is a grade IV astrocytoma and the most common form of malignant brain tumor in adults. GBM remains one of the most fatal and least successfully treated solid tumors: current therapies provide a median survival of 12–15 months after diagnosis, due to the high recurrence rate. Glioma Stem Cells (GSCs) are believed to be the real driving force of tumor initiation, progression and relapse. Therefore, better therapeutic strategies GSCs-targeted are needed. Resveratrol is a polyphenolic phytoalexin found in fruits and vegetables displaying pleiotropic health benefits. Many studies have highlighted its chemo-preventive and chemotherapeutic activities in a wide range of solid tumors. In this work, we analyzed the effects of Resveratrol exposure on cell viability, proliferation and motility in seven GSC lines isolated from GBM patients. For the first time in our knowledge, we investigated Resveratrol impact on Wnt signaling pathway in GSCs, evaluating the expression of seven Wnt signaling pathway-related genes and the protein levels of c-Myc and β-catenin. Finally, we analyzed Twist1 and Snail1 protein levels, two pivotal activators of epithelial-mesenchymal transition (EMT) program.Results showed that although response to Resveratrol exposure was highly heterogeneous among GSC lines, generally it was able to inhibit cell proliferation, increase cell mortality, and strongly decrease cell motility, modulating the Wnt signaling pathway and the EMT activators. Treatment with Resveratrol may represent a new interesting therapeutic approach, in order to affect GSCs proliferation and motility, even if further investigations are needed to deeply understand the GSCs heterogeneous response.

Resveratrol in Cancer Patients: From Bench to Bedside

“…Such a bond allows p53 to definitely block the cell replication phase [81][82][83]. It emerged that resveratrol is able to induce the tumor cell cycle blockade also via inhibition of other intracellular signals such as Wnt/β-catenin, Hippo-YAP and Hedgehog that synergistically concur to tumor development, invasion and metastasis [54,[84][85][86]. These pathways are also implicated in epithelial mesenchymal transition (EMT), a process conferring epithelial cells with mesenchymal characteristics necessary for tumor invasion.…”

Targeting cancer stem cells and signaling pathways by resveratrol and pterostilbene

“…Cilibrasi et al investigated the efficacy of resveratrol on GSCs using seven established lines, which possess extensive stem‐like properties . In these researchers’ studies, resveratrol generally decreased GSCs viability and proliferation and inhibited GSCs motility and invasion.…”

Traditional Chinese medicine as a cancer treatment: Modern perspectives of ancient but advanced science

“…Glioma stem cell↓; Cervical cancer stem cells↓; Breast cancer stem cells↓; Colon cancer stem cells↓; Leukemia stem cell↓…”