Department of Medical Biochemistry, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
Student Research Committee, Faculty of Medicine, North Khorasan University of Medical Sciences, Bojnurd, Iran.
Oxid Med Cell Longev. 2020 May 6;2020:3237983. doi: 10.1155/2020/3237983. eCollection 2020.
Glioblastoma multiforme (GBM) is the most hostile tumor in the central nervous system. Unfortunately, the prognosis of GBM patients is poor following surgical interventions, chemotherapy, and radiotherapy. Consequently, more efficient and effective treatment options for the treatment of GBM need to be explored. Zerumbone, as a sesquiterpene derived from Smith, has substantial cytotoxic and antiproliferative activities in some types of cancer. Here, we show that exposure of GBM cells (U-87 MG) to Zerumbone demonstrated significant growth inhibition in a concentration-dependent manner. Zerumbone also induced apoptosis and caused cell cycle arrest of human GBM U-87 MG cells in the G2/M phase of the cell cycle. In detail, the apoptotic process triggered by Zerumbone involved the upregulation of proapoptotic Bax and the suppression of antiapoptotic Bcl-2 genes expression as determined by qRT-PCR. Moreover, Zerumbone enhanced the generation of reactive oxygen species (ROS), and N-acetyl cysteine (NAC), as an antioxidant, reversed the ROS-induced cytotoxicity of U-87 MG cells. The Western blot analysis suggested that Zerumbone activated the NF-B p65, which was partly inhibited by NAC treatment. Collectively, our results confirmed that Zerumbone induces cytotoxicity by ROS generation. Thus, the study raises the possibility of Zerumbone as a potential natural agent for treating GBM due to its ability to induce cytotoxicity.
胶质母细胞瘤（GBM）是中枢神经系统中最具侵袭性的肿瘤。不幸的是，GBM 患者在接受手术干预、化疗和放疗后预后较差。因此，需要探索更有效和有效的治疗 GBM 的方法。姜烯，一种来源于 Smith 的倍半萜烯，在某些类型的癌症中具有显著的细胞毒性和抗增殖活性。在这里，我们表明，GBM 细胞（U-87 MG）暴露于 Zerumbone 表现出浓度依赖性的显著生长抑制。Zerumbone 还诱导人 GBM U-87 MG 细胞的细胞凋亡并导致细胞周期停滞在细胞周期的 G2/M 期。具体而言，由 Zerumbone 触发的凋亡过程涉及促凋亡 Bax 的上调和抗凋亡 Bcl-2 基因表达的抑制，这是通过 qRT-PCR 确定的。此外，Zerumbone 增强了活性氧（ROS）的产生，N-乙酰半胱氨酸（NAC）作为抗氧化剂，逆转了 U-87 MG 细胞中 ROS 诱导的细胞毒性。Western blot 分析表明，Zerumbone 激活了 NF-B p65，而 NAC 处理部分抑制了 NF-B p65 的激活。总之，我们的研究结果证实，Zerumbone 通过产生 ROS 诱导细胞毒性。因此，由于其诱导细胞毒性的能力，该研究提出了将 Zerumbone 作为治疗 GBM 的潜在天然药物的可能性。
