Grincamycin B Functions as a Potent Inhibitor for Glioblastoma Stem Cell via Targeting RHOA and PI3K/AKT.,ACS Chemical Neuroscience

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Grincamycin B Functions as a Potent Inhibitor for Glioblastoma Stem Cell via Targeting RHOA and PI3K/AKT.
ACS Chemical Neuroscience ( IF 4.1 ) Pub Date : 2020-06-25 , DOI: 10.1021/acschemneuro.0c00206
Yueliang Yao ₁ , Si Sun ₂ , Mianfu Cao ₁ , Min Mao ₁ , Jiang He ₁ , Qujing Gai ₁ , Yan Qin ₁ , Xiaoxue Yao ₁ , Huimin Lu ₁ , Fanglin Chen ₁ , Wenying Wang ₁ , Min Luo _{1,

3} , Hua Zhang _{1,

3} , Hongbo Huang ₄ , Jianhua Ju ₄ , Xiu-Wu Bian ₁ , Yan Wang ₁

Affiliation

Glioblastoma multiforme (GBM) is the most malignant form of glioma, and the overall survival time of patients with GBM is usually less than 14 months. Therefore, it is urgent to find new and effective medicine for GBM. Recently, marine natural products have been shown to exhibit strong inhibitory effects on cancer cells, providing a new avenue for exploring novel drugs for GBM treatment. In this study, we investigated the inhibitory effect of the Grincamycin (GCN) B–F, newly isolated from marine-derived Streptomyces Lusitanus SCSIO LR32, on GBM cells, and evaluated the mechanism of GCN B on GBM. The results, for the first time, showed that GCN B acted as a potent inhibitor to suppress growth and invasion of two human GBM cell lines U251 and 091214 in vitro. In addition, GCN B could effectively target GSCs in GBM evidenced by attenuated formation of tumor spheres and decrease of several markers of GSCs. Furthermore, we performed gene expression microarray followed by Signal-Net analysis. The result revealed that RHOA and PI3K/AKT axis played critical roles for a GCN B-mediated inhibitory effect on GSCs. Altogether, our findings highlighted GCN B as a promising inhibitor for GSCs via targeting RHOA and PI3K/AKT.

中文翻译：

格林卡霉素B通过靶向RHOA和PI3K / AKT作为胶质母细胞瘤干细胞的有效抑制剂。

多形胶质母细胞瘤（GBM）是神经胶质瘤的最恶性形式，GBM患者的总体生存时间通常少于14个月。因此，迫切需要为GBM寻找新的有效药物。最近，海洋天然产物已显示出对癌细胞的强抑制作用，为探索用于GBM的新药物提供了新途径。在这项研究中，我们研究了从海洋源链霉菌Lusitanus SCSIO LR32中新分离出的格林霉素（GCN）B–F对GBM细胞的抑制作用，并评估了GCN B对GBM的作用。结果，在第一次，表明GCN乙充当有效的抑制剂以抑制生长和两种人GBM细胞系U251的入侵和091214在体外。此外，GCN B可以有效地靶向GBM中的GSC，这是由肿瘤球形成的减弱和GSC几种标志物的减少所证明的。此外，我们进行了基因表达微阵列，然后进行Signal-Net分析。结果表明，RHOA和PI3K / AKT轴在GCN B介导的GSC抑制作用中起着关键作用。总而言之，我们的发现突出了GCN B通过靶向RHOA和PI3K / AKT成为GSC的有希望的抑制剂。

更新日期：2020-08-05

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