Protein Chemistry Center and Department of Cell and Molecular Biology and Pathogenic Bioagents, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, SP 14049-900, Brazil.
Department of Biochemistry and Immunology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, SP 14040-900, Brazil.
Int J Mol Sci. 2020 Jul 1;21(13):4713. doi: 10.3390/ijms21134713.
Gliomas are responsible for more than 60% of all primary brain tumors. Glioblastoma multiforme (GBM), a grade IV tumor (WHO), is one of the most frequent and malignant gliomas. Despite two decades of advances in the discovery of new markers for GBM, the chemotherapy of choice falls to temozolomide after surgery and radiotherapy, which are not enough to increase the survival of patients to more than 15 months. It is urgent to discover new anti-glioma compounds. Many compounds derived from natural products have been used in the development of anti-tumor drugs. In this work, we have screened six low molecular weight sesquiterpene lactones, isolated from spp., and studied their function as anti-proliferative agents against GBM strains. We demonstrated that two of them, goyazensolide and lychnofolide, were effective in reducing cell viability, preventing the formation of anchorage-dependent colony and were able to pass through a mimetic blood-brain barrier making them candidates for glioma therapy, being more potent than temozolomide, according to in vitro assays for the cell lines tested. Proteomic analysis revealed a number of altered proteins involved in glycolytic metabolism and cellular catabolism.
神经胶质瘤导致了超过 60%的原发性脑肿瘤。多形性胶质母细胞瘤（GBM），一种 4 级肿瘤（世界卫生组织），是最常见和恶性的神经胶质瘤之一。尽管在发现 GBM 的新标志物方面取得了二十年的进展，但手术后和放疗后的首选化疗药物仍是替莫唑胺，这不足以将患者的生存时间延长到 15 个月以上。迫切需要发现新的抗神经胶质瘤化合物。许多源自天然产物的化合物已被用于抗肿瘤药物的开发。在这项工作中，我们筛选了从 种中分离出的六种低分子量倍半萜内酯，并研究了它们作为抗 GBM 株增殖剂的功能。我们证明其中两种，goyazensolide 和 lychnofolide，能够有效降低细胞活力，阻止锚定依赖性集落的形成，并能够穿透模拟血脑屏障，使它们成为神经胶质瘤治疗的候选药物，根据对测试细胞系的体外测定，其效果强于替莫唑胺。蛋白质组学分析揭示了许多涉及糖酵解代谢和细胞分解代谢的改变蛋白。
