Department of Environmental, Biological and Pharmaceutical Sciences and Technologies, University of Campania "Luigi Vanvitelli", 81100 Caserta, Italy.
Institute of Genetics and Biophysics "A. Buzzati Traverso" (IGB-ABT), National Research Council, 16149 Naples, Italy.
Int J Mol Sci. 2024 Nov 2;25(21):11789. doi: 10.3390/ijms252111789.
Glioblastoma (GBM) is the most aggressive type of brain tumor, characterized by poor outcome and limited therapeutic options. During tumor progression, GBM may undergo the process of vasculogenic mimicry (VM), consisting of the formation of vascular-like structures which further promote tumor aggressiveness and malignancy. The resulting resistance to anti-angiogenetic therapies urges the identification of new compounds targeting VM. Extracts of natural plants may represent potential therapeutic tools. Among these, components of water extract (RGWE) display a wide range of biological activities. To test the effect of RGWE on human GBM and rat glioma cell line VM, tube formation on a gelled matrix was monitored. Quantitative assessment of VM formation shows the clear-cut inhibitory activity of RGWE. Unlike rutin, one of the most abundant extract components, the whole RGWE strongly reduced the migration and invasion of GBM tumor cells. Moreover, RGWE induced cell death of GBM patient-derived cancer stem cells and impaired VM at sub-lethal doses. Overall, our data reveal a marked RGWE-dependent inhibition of GBM cell survival, migration, invasion, and VM formation. Thus, the clear-cut ability of RGWE to counteract GBM malignancy deserves attention, holding the promise to bring natural products to clinical use, thus uncovering new therapeutic opportunities.
胶质母细胞瘤（GBM）是最具侵袭性的脑肿瘤，其预后不良且治疗选择有限。在肿瘤进展过程中，GBM 可能经历血管生成拟态（VM）过程，包括形成类似血管的结构，从而进一步促进肿瘤侵袭性和恶性程度。由此产生的对血管生成抑制剂治疗的耐药性促使人们寻找新的针对 VM 的化合物。天然植物提取物可能代表潜在的治疗工具。其中，水提取物（RGWE）的成分具有广泛的生物活性。为了测试 RGWE 对人 GBM 和大鼠神经胶质瘤细胞系 VM 的影响，监测了在凝胶基质上形成的管状结构。VM 形成的定量评估显示 RGWE 具有明显的抑制活性。与作为最丰富的提取物成分之一的芦丁不同，整个 RGWE 强烈抑制了 GBM 肿瘤细胞的迁移和侵袭。此外，RGWE 诱导源自 GBM 患者的癌症干细胞死亡，并在亚致死剂量下破坏 VM。总的来说，我们的数据揭示了 RGWE 对 GBM 细胞存活、迁移、侵袭和 VM 形成的明显抑制作用。因此，RGWE 明显抑制 GBM 恶性的能力值得关注，有望将天然产物应用于临床，从而为治疗提供新的机会。
