Raddeanin a Suppresses Glioblastoma Growth by Inducing ROS Generation and Subsequent JNK Activation to Promote Cell Apoptosis
Raddeanin a Suppresses Glioblastoma Growth by Inducing ROS Generation and Subsequent JNK Activation to Promote Cell Apoptosis
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Raddeanin a 通过诱导 ROS 生成和随后的 JNK 激活促进细胞凋亡来抑制胶质母细胞瘤生长
DOI：
10.1159/000490187
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发表时间：
2018-01-01
影响因子：
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通讯作者：
Zhao, Shiguang
中科院分区：
文献类型：
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作者：
Peng, Eel;Wang, Xiaoxiong;Zhao, Shiguang
背景/目的：海葵苷A （Raddeanin A， RA）是海葵的一种有效药理成分，具有重要的肿瘤抑制作用。在这项研究中，我们评估了类风湿性关节炎对胶质母细胞瘤的潜在治疗作用及其潜在机制。方法：采用MTT法检测细胞活力。采用Transwell和伤口愈合试验检测侵入性和迁移能力。采用Hoechst染色、流式细胞术、dcfh荧光探针和免疫组化染色检测细胞凋亡。透射电镜和免疫印迹法检测细胞自噬。建立U251胶质瘤异种移植模型，在体内评价RA的作用。结果：类风湿关节炎抑制胶质母细胞瘤细胞的生存能力，破坏胶质母细胞瘤细胞的侵袭/迁移能力。此外，RA通过活性氧(ROS)/ Jun n -末端激酶（JNK）信号通路诱导胶质母细胞瘤细胞凋亡。相反，抗氧化剂n-乙酰- l-半胱氨酸（NAC）和泛caspase抑制剂z-VAD-fmk通过清除ROS和灭活caspase-3来减轻ra诱导的细胞凋亡。此外，3-MA对自噬的抑制通过ROS生成和JNK磷酸化加剧了细胞凋亡。在体内，RA对裸鼠u251来源的异种移植物有疗效。结论：本研究结果提示RA可抑制胶质母细胞瘤的生长，因此可作为一种有前景和潜在的胶质母细胞瘤化疗策略。
Background/Aims: Raddeanin A (RA), an active pharmacological ingredient from Anemone raddeana Regel, plays an important role in tumor suppression. In this study, we assessed the potentially therapeutic effect of RA on glioblastoma and its underlying mechanisms. Methods: Cell viability was examined using the MTT assay. Invasive and migratory capacities were examined using Transwell and wound healing assays. Apoptosis was determined by Hoechst staining, flow cytometry, DCFH-fluorescent probe and immunohistochemical staining. Autophagy was detected by transmission electron microscopy and western blotting. A U251 glioma xenograft model was established to evaluate the effect of RA in vivo. Results: The data demonstrated that RA inhibited viability, and abrogated the invasive/migratory abilities of glioblastoma cells. In addition, RA induced apoptosis by reactive oxygen species (ROS)/ Jun N-terminal kinase (JNK) signaling in glioblastoma. Conversely, the antioxidant N-Acetyl-L-cysteine (NAC) and pan-caspase inhibitor z-VAD-fmk attenuated RA-induced apoptosis by scavenging ROS and inactivating caspase-3. Furthermore, the inhibition of autophagy by 3-MA exacerbated apoptosis through ROS generation and JNK phosphorylation. In vivo, RA exhibited a curative effect on U251-derived xenografts in nude mice. Conclusions: The results of this study suggest that RA suppressed the growth of glioblastoma, thus serving as a promising and potential strategy for glioblastoma chemotherapy.