A Proteomic Platform Unveils the Brain Glycogen Phosphorylase as a Potential Therapeutic Target for Glioblastoma Multiforme

Abstract

In the last few years, several efforts have been made to identify original strategies against glioblastoma multiforme (GBM): this requires a more detailed investigation of the molecular mechanism of GBM so that novel targets can be identified for new possible therapeutic agents. Here, using a combined biochemical and proteomic approach, we evaluated the ability of a blood–brain barrier-permeable 2,3-benzodiazepin-4-one, called 1g, to interfere with the activity and the expression of brain glycogen phosphorylase (PYGB) on U87MG cell line in parallel with the capability of this compound to inhibit the cell growth and cycle. Thus, our results highlighted PYGB as a potential therapeutic target in GBM prompting 1g as a capable anticancer drug thanks to its ability to negatively modulate the uptake and metabolism of glucose, the so-called “Warburg effect”, whose increase is considered a common feature of cancer cells in respect of their normal counterparts.

Brain-Type Glycogen Phosphorylase (PYGB) in the Pathologies of Diseases: A Systematic Review

“…The results highlighted PYGB as a potential therapeutic target for U87MG of GBM and indicated that 2,3-benzodiazepin-4-one can be used to develop anti-cancer drugs for glioblastoma because it can negatively regulate glucose uptake and metabolism (the "Warburg effect") [63].…”

Screening and Analysis of Possible Drugs Binding to PDGFRα: A Molecular Modeling Study

“…Twenty-seven molecules were mainly selected on the basis of the best binding energies obtained from the results of the MTiOpenScreen web server. To check these results, we carried out a further docking analysis using the SwissDock web server, as previously reported [38], based on the EADock DSS algorithm [39,40], and setting the docking type as accurate without a definition of the region of interest to include the whole protein in the search space. The final geometry of the complexes obtained was rendered by PyMol software (The PyMOL Molecular Graphics System, Version 2.5.2, Schrödinger, LLC., Cambridge, MA, USA), and the 3D representation of the interaction was obtained by the Protein-Ligand Interaction Profiler (PLIP) web server [41].…”

Advances in Immunotherapy and Innovative Therapeutic Approaches for Cancer Treatment: Editorial to the Special Issue “State-of-the-Art Molecular Oncology in Italy”

“…Ferraro et al have characterized a novel potential therapeutic target for the treatment of glioblastoma multiforme (GBM) [17]. In their study, the authors identified brain glycogen phosphorylase (PYGB) as a valid molecular target for the treatment of GBM, which catalyzes the transformation from glycogen to glucose 1-phosphate and supports glucose metabolism in cancer cells (the so-called "Warburg effect").…”

“…In their study, the authors identified brain glycogen phosphorylase (PYGB) as a valid molecular target for the treatment of GBM, which catalyzes the transformation from glycogen to glucose 1-phosphate and supports glucose metabolism in cancer cells (the so-called "Warburg effect"). The results of a combined biochemical and proteomic analysis revealed that PYGB could be targeted in different GBM cell lines and primary neuronal cells via 2,3-benzodiazepin-4-one, a blood-brain barrier-permeating compound, also known as 1g, that interferes with cancer cell metabolism [17].…”