Tsafa Effrosyni, Dimitriadis Kyriakos, Kalampoki Lamprini, Papapetrou Panagiota, Georgalis Pavlos A, Bozios Georgios, Sioka Chrissa, Tsekeris Pericles, Kyritsis Athanassios P, Alexiou George A, Lazari Diamanto
Neurosurgical Institute, University of Ioannina, 451 10 Ioannina, Greece.
Laboratory of Pharmacognosy, School of Pharmacy, Faculty of Health Sciences, Aristotle University of Thessaloniki, 541 24 Thessaloniki, Greece.
Biomedicines. 2024 Dec 9;12(12):2793. doi: 10.3390/biomedicines12122793.
BACKGROUND/OBJECTIVES: Glioblastoma (GBM) is the most aggressive type of brain tumor in adults. Currently, the only treatments available are surgery, radiotherapy, and chemotherapy based on temozolomide (TMZ); however, the prognosis is dismal. Several natural substances are under investigation for cancer treatment. 8α-O-(3,4-dihydroxy-2-methylenebutanoyloxy) dehydromelitensine (Isocnicin) is a natural compound derived from species and was found to exhibit cytostatic/cytotoxic effect against different cell lines. In this study, we investigated the anti-glioma effects of isocnicin in U87 and T98 glioblastoma cell lines, as well as the effects of combined treatment with radiotherapy.
Cell viability was evaluated with the trypan blue exclusion assay, cell cycle distribution was examined using flow cytometry, and the effects of the combination treatment were analyzed with CompuSyn software(1.0).
The result showed that isocnicin significantly reduced cell viability in U87 and T98 cell lines in a dose-dependent manner and IC values were calculated. Administration of isocnicin alone induced both S and G2/M cell cycle arrest in U87 and T98 cells in a dose-dependent manner. Moreover, when cells were treated with increasing concentrations of isocnicin, followed by 2 or 4 Gy of radiation, the percentage distribution of the cells in the G2/M phase was increased considerably in both U87 and T98 cell lines.
Here, we show for the first time that co-treatment of isocnicin with radiation exerts a synergistic antiproliferative effect in glioblastoma cell lines. Natural compounds are promising for glioblastoma treatment. Further studies will be necessary to unravel isocnicin's mechanism of action and its synergistic effect with radiation on glioblastoma treatment.
背景/目的：胶质母细胞瘤（GBM）是成人中最具侵袭性的脑肿瘤类型。目前，唯一可用的治疗方法是手术、放疗以及基于替莫唑胺（TMZ）的化疗；然而，预后很差。几种天然物质正在进行癌症治疗方面的研究。8α - O -（3,4 - 二羟基 - 2 - 亚甲基丁酰氧基）脱氢美登素（异美登素）是一种从[具体物种]衍生的天然化合物，已发现其对不同细胞系具有细胞生长抑制/细胞毒性作用。在本研究中，我们研究了异美登素对U87和T98胶质母细胞瘤细胞系的抗胶质瘤作用，以及与放疗联合治疗的效果。
用台盼蓝排斥试验评估细胞活力，用流式细胞术检测细胞周期分布，并用CompuSyn软件（1.0）分析联合治疗的效果。
结果表明，异美登素以剂量依赖性方式显著降低U87和T98细胞系的细胞活力，并计算了IC值。单独给予异美登素以剂量依赖性方式诱导U87和T98细胞的S期和G2/M期细胞周期阻滞。此外，当用浓度递增的异美登素处理细胞后再给予2或4 Gy辐射时，U87和T98细胞系中G2/M期细胞的百分比分布均显著增加。
在此，我们首次表明异美登素与放疗联合治疗在胶质母细胞瘤细胞系中发挥协同抗增殖作用。天然化合物在胶质母细胞瘤治疗方面具有前景。有必要进一步研究以阐明异美登素的作用机制及其与放疗在胶质母细胞瘤治疗中的协同作用。
