Giannakopoulou Maria, Dimitriadis Kiriakos, Koromili Maria, Zoi Vasiliki, Vartholomatos Evrysthenis, Galani Vasiliki, Kyritsis Athanassios P, Alexiou George A, Lazari Diamanto
Neurosurgical Institute, University of Ioannina, 45500 Ioannina, Greece.
Laboratory of Pharmacognosy, Division of Pharmacognosy-Pharmacology, School of Pharmacy, Faculty of Health Sciences, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece.
Biomedicines. 2022 Dec 12;10(12):3216. doi: 10.3390/biomedicines10123216.
Glioblastoma (GBM) is the most aggressive primary central nervous system (CNS) tumor in adults with dismal prognosis. Currently, the therapeutic interventions include gross total resection, when possible, followed by radiotherapy and chemotherapy. However, despite treatment, tumor usually recurs within 7-9 months. The presence of glioma cells with stem-like properties and tumor's heterogeneity have been identified as the most important factors driving recurrence. Recently, research efforts have been focused on the use of natural substances as treatment for GBM. Siderol is an ent-kaurane diterpenoid, isolated from the genus . extracts have already been investigated for their anti-inflammatory, antioxidant, and anticancer effects. In this study, we investigated the antitumoral effects of siderol in GBM T98 and U87 cell lines, as well as the effects of combined treatment with temozolomide (TMZ). Cell viability was evaluated by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and trypan blue exclusion assay. Different concentrations of siderol were used in order to calculate the IC50 values at 72 h after treatment. Flow cytometry used for the DNA cell cycle analysis after treatment with siderol in concentrations of IC50 and twice the IC50 values for 72 h. Furthermore, the effect of siderol in cell's migratory ability was tested using wound healing assay. Cell viability and proliferation, after combined treatment with siderol and TMZ, also were evaluated with the trypan blue exclusion assay and the effects of the combination treatment were analyzed with CompuSyn software. Treatment with siderol significantly reduced cell viability in T98 and U87 cell lines in a dose-dependent manner and IC50 values were calculated, 18 μM and 13 μM, respectively. Moreover, siderol induced G/G cell cycle arrest in a dose-dependent manner and inhibited the migration in both cell lines. In addition, siderol and TMZ seem to have synergistic action in the majority of tested concentrations in both T98 and U87 cells. In conclusion, siderol may represent an innovative strategy for the treatment of GBM, and further studies are needed on siderol's efficacy and mode of action.
胶质母细胞瘤（GBM）是成人中最具侵袭性的原发性中枢神经系统（CNS）肿瘤，预后极差。目前，治疗干预措施包括在可能的情况下进行全切除，然后进行放疗和化疗。然而，尽管进行了治疗，肿瘤通常在7 - 9个月内复发。具有干细胞样特性的胶质瘤细胞的存在以及肿瘤的异质性已被确定为驱动复发的最重要因素。最近，研究工作集中在使用天然物质治疗GBM。西德罗尔是一种对映贝壳杉烷二萜，从该属中分离出来。其提取物已被研究具有抗炎、抗氧化和抗癌作用。在本研究中，我们研究了西德罗尔对GBM T98和U87细胞系的抗肿瘤作用，以及与替莫唑胺（TMZ）联合治疗的效果。通过3 -（4,5 - 二甲基噻唑 - 2 - 基）- 2,5 - 二苯基四氮唑溴盐（MTT）法和台盼蓝排斥试验评估细胞活力。使用不同浓度的西德罗尔以计算治疗72小时后的IC50值。在以IC50浓度和两倍IC50值处理西德罗尔72小时后，使用流式细胞术进行DNA细胞周期分析。此外，使用伤口愈合试验测试西德罗尔对细胞迁移能力的影响。在西德罗尔与TMZ联合治疗后，也通过台盼蓝排斥试验评估细胞活力和增殖，并使用CompuSyn软件分析联合治疗的效果。用西德罗尔治疗以剂量依赖性方式显著降低了T98和U87细胞系中的细胞活力，并计算出IC50值分别为18μM和13μM。此外，西德罗尔以剂量依赖性方式诱导G/G细胞周期停滞并抑制两种细胞系中的迁移。此外，在T98和U87细胞的大多数测试浓度下，西德罗尔和TMZ似乎具有协同作用。总之，西德罗尔可能代表一种治疗GBM的创新策略，需要对西德罗尔的疗效和作用方式进行进一步研究。
