Department of Pharmacy, University of Salerno, 84084 Fisciano, Italy.
PhD Program in Drug Discovery and Development, Department of Pharmacy, University of Salerno, 84084 Fisciano, Italy.
Int J Mol Sci. 2022 Jul 25;23(15):8200. doi: 10.3390/ijms23158200.
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.
在过去的几年中，人们已经做出了一些努力来确定针对多形性胶质母细胞瘤（GBM）的原始策略：这需要更详细地研究 GBM 的分子机制，以便为新的可能治疗剂确定新的靶标。在这里，我们使用联合生化和蛋白质组学方法，评估了一种血脑屏障通透性的 2,3-苯并二氮杂酮，称为 1g，在与该化合物抑制细胞生长和周期的能力平行的情况下，干扰 U87MG 细胞系中脑糖原磷酸化酶（PYGB）活性和表达的能力。因此，我们的结果强调了 PYGB 作为 GBM 的潜在治疗靶标，并促使 1g 成为一种有能力的抗癌药物，这要归功于其能够负调控葡萄糖的摄取和代谢，即所谓的“Warburg 效应”，其增加被认为是癌细胞相对于正常细胞的一个共同特征。
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