Sparstolonin B, a novel plant derived compound, arrests cell cycle and induces apoptosis in N-myc amplified and N-myc nonamplified neuroblastoma cells.
Sparstolonin B, a novel plant derived compound, arrests cell cycle and induces apoptosis in N-myc amplified and N-myc nonamplified neuroblastoma cells.
复制标题
DOI：
10.1371/journal.pone.0096343
复制
发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Singh US
中科院分区：
文献类型：
--
作者：
Kumar A;Fan D;Dipette DJ;Singh US
神经母细胞瘤是最常见的实体瘤之一，占儿童所有癌症相关死亡的15%。尽管晚期疾病的标准治疗包括化疗、手术和放疗，但这些患者的死亡率仍然很高。因此，迫切需要新的治疗剂。在这里，我们使用不同遗传学的神经母细胞瘤细胞系检测了一种新的植物衍生化合物，sparstolonin B（Ssn B; 8，5 ′-dihydroxy-4-phenyl-5，2 ′-oxidoisocoumarin）的抗癌活性。SsnB最近从一种水生中草药三棱中分离出来，该草药的块茎已在中药中用于治疗多种炎症性疾病和癌症。我们的细胞活力和形态学分析表明，10 µM浓度的SsnB显著抑制N-myc扩增（SK-N-BE（2）、NGP和IMR-32细胞）和N-myc非扩增（SH-SY 5 Y和SKNF-1细胞）神经母细胞瘤细胞的生长。流式细胞仪分析表明，SsnB阻滞细胞周期进程在G2-M期在所有测试的神经母细胞瘤细胞系。体外三维细胞培养实验（贴壁非依赖性集落形成实验和悬滴实验）显示，SsnB可抑制SH-SY 5 Y细胞和SK-N-BE（2）细胞形成致密球状体，降低其致瘤性。SsnB降低谷胱甘肽（GSH）的细胞水平，增加活性氧物质的产生并激活半胱天冬酶-3的裂解，而GSH前体N-乙酰半胱氨酸与SsnB沿着的共孵育减弱了SsnB的抑制作用并增加了神经母细胞瘤细胞的存活力。我们的研究结果首次表明，SsnB具有抗癌活性，表明SsnB诱导的活性氧生成促进不同遗传背景的神经母细胞瘤细胞的凋亡细胞死亡。因此，这些数据表明，SsnB可以是一个有前途的候选药物在神经母细胞瘤治疗。
Neuroblastoma is one of the most common solid tumors and accounts for ∼15% of all the cancer related deaths in the children. Despite the standard therapy for advanced disease including chemotherapy, surgery, and radiation, the mortality rate remains high for these patients. Hence, novel therapeutic agents are desperately needed. Here we examined the anticancer activity of a novel plant-derived compound, sparstolonin B (SsnB; 8,5′-dihydroxy-4-phenyl-5,2′-oxidoisocoumarin) using neuroblastoma cell lines of different genetics. SsnB was recently isolated from an aquatic Chinese herb, Sparganium stoloniferum, and tubers of this herb have been used in traditional Chinese medicine for the treatment of several inflammatory diseases and cancers. Our cell viability and morphological analysis indicated that SsnB at 10 µM concentration significantly inhibited the growth of both N-myc amplified (SK-N-BE(2), NGP, and IMR-32 cells) and N-myc nonamplified (SH-SY5Y and SKNF-1 cells) neuroblastoma cells. The flow cytometric analyses suggested that SsnB arrests the cell cycle progression at G2-M phase in all neuroblastoma cell lines tested. Exposure of SsnB inhibited the compact spheroid formation and reduced the tumorigenicity of SH-SY5Y cells and SK-N-BE(2) cells in in vitro 3-D cell culture assays (anchorage-independent colony formation assay and hanging drop assay). SsnB lowers the cellular level of glutathione (GSH), increases generation of reactive oxygen species and activates the cleavage of caspase-3 whereas co-incubation of a GSH precursor, N-acetylcysteine, along with SsnB attenuates the inhibitory effects of SsnB and increases the neuroblastoma cell viability. Our results for the first time demonstrate that SsnB possesses anticancer activity indicating that SsnB-induced reactive oxygen species generation promotes apoptotic cell death in neuroblastoma cells of different genetic background. Thus these data suggest that SsnB can be a promising drug candidate in neuroblastoma therapy.
登录
查看更多内容
影响因子：
6.7
作者：
Lee, Seung Young;Choi, Sang Un;Lee, Kang Ro
通讯作者：
Lee, Kang Ro
DOI：
10.1111/j.1530-0277.2010.01166.x
发表时间：
2010-05-01
影响因子：
3.2
作者：
Kumar, Ambrish;Singh, Chandra K.;Singh, Ugra S.
通讯作者：
Singh, Ugra S.
Sparstolonin B 抑制脂多糖诱导的人脐静脉内皮细胞炎症
影响因子：
6.7
作者：
Liang, Qiaoli;Yu, Fang;Cui, Xiaodong;Duan, Jin'ao;Wu, Qinan;Nagarkatti, Prakash;Fan, Daping
通讯作者：
Fan, Daping
影响因子：
56.9
作者：
BRODEUR, GM;SEEGER, RC;BISHOP, JM
通讯作者：
BISHOP, JM
影响因子：
3.6
作者：
Kumar, Ambrish;Singh, Chandra K.;Singh, Ugra S.
通讯作者：
Singh, Ugra S.