Glioblastoma multiforme (GBM) is the most common and aggressive type of malignant primary brain tumor, and it is characterized by a high recurrence incidence and poor prognosis due to the presence of a highly heterogeneous mass of stem cells with self-renewal capacity and stemness maintenance ability. In recent years, the epigenetic landscape of GBM has been explored and many epigenetic alterations have been investigated. Among the investigated epigenetic abnormalities, the bromodomain and extra-terminal domain (BET) chromatin readers have been found to be significantly overexpressed in GBM. In this work, we investigated the effects of BET protein inhibition on GBM cell reprogramming. We found that the pan-BET pharmacological inhibitor JQ1 was able to promote a differentiation program in GBM cells, thus impairing cell proliferation and enhancing the toxicity of the drug Temozolomide (TMZ). Notably, the pro-differentiation capability of JQ1 was prevented in autophagy-defective models, suggesting that autophagy activation is necessary for BET protein activity in regulating glioma cell fate. Given the growing interest in epigenetic therapy, our results further support the possibility of introducing a BET-based approach in GBM clinical management.

BET proteins are a family of multifunctional epigenetic readers, mainly involved in transcriptional regulation through chromatin modelling. Transcriptome handling ability of BET proteins suggests a key role in the modulation of cell plasticity, both in fate decision and in lineage commitment during embryonic development and in pathogenic conditions, including cancerogenesis. Glioblastoma is the most aggressive form of glioma, characterized by a very poor prognosis despite the application of a multimodal therapy. Recently, new insights are emerging about the glioblastoma cellular origin, leading to the hypothesis that several putative mechanisms occur during gliomagenesis. Interestingly, epigenome dysregulation associated with loss of cellular identity and functions are emerging as crucial features of glioblastoma pathogenesis. Therefore, the emerging roles of BET protein in glioblastoma onco-biology and the compelling demand for more effective therapeutic strategies suggest that BET family members could be promising targets for translational breakthroughs in glioblastoma treatment. Primarily, “Reprogramming Therapy”, which is aimed at reverting the malignant phenotype, is now considered a promising strategy for GBM therapy.

Glioblastoma (GBM) is the most common and aggressive form of brain cancer in adults, characterized by extensive growth, a high recurrence rate, and resistance to treatment. Growing research interest is focusing on the biological roles of natural compounds due to their potential beneficial effects on health. Our research aimed to investigate the effects of lavender essential oil (LEO) on a GBM cell model. Chemical characterization using GC-MS analysis indicated that LEO contains several terpenes, compounds that have been found to exhibit anticancer properties by interfering with key cancer-related pathways in several cancer models. By means of cell biology assays, we demonstrated that LEO impairs cell proliferation and migration, and also reduces oxidative stress in U87 cells. We further observed that Terpinen-4-ol, contained in LEO, was capable of reproducing the effects of the oil on GBM cells. Our results suggest that the terpenic molecules present in LEO could be considered valuable allies alongside conventional therapies against GBM.

Aberrant sialylation has been associated with many types of tumors, characterized by aggressiveness and undifferentiated state. However, not exhaustive investigations have been performed on the sialylation status in glioblastoma multiforme (GBM), the most common primary and lethal malignant brain tumor in humans. Hence, in this study we performed a comprehensive characterization of the sialylation status in GBM evaluating specific sialyltransferases and various types of sialic acids (Sias) in different GBM cell lines. First, through in silico analysis we showed that the sialyltransferases ST6GAL1, ST3GAL2 and ST8SIA4 are significantly up-regulated in GBM tissues and related to lower patient survival. Then, we evaluated the expression levels of these sialyltransferases and their related Sias and observed a high variability among the different GBM cell lines. In addition, using the pan-sialyltransferase inhibitor 3-Fax, we highlighted the role of sialylation in some of the main oncogenic properties of GBM. Indeed, a significant reduction in mobility and migration capacity along with increased adhesiveness of GBM cells was observed upon sialyltransferases inhibition. Our findings showed that aberrant expression of different Sias types is crucial for cell migration and adhesion ability of GBM cells, suggesting that Sias might represent biomarkers for GBM and be useful to design innovative therapeutic strategies.