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A pipecolic acid-rich branched cyclic depsipeptide ulleungamide C from a Streptomyces species induces G0/G1 cell cycle arrest in promyelocytic leukemia cells
The Journal of Antibiotics ( IF 2.1 ) Pub Date : 2020-11-18 , DOI: 10.1038/s41429-020-00385-z
Sangkeun Son 1, 2 , Mina Jang 1 , Byeongsan Lee 1 , Jun-Pil Jang 1 , Young-Soo Hong 1, 3 , Bo Yeon Kim 1, 3 , Sung-Kyun Ko 4 , Jae-Hyuk Jang 3, 4 , Jong Seog Ahn 1, 3
Affiliation  

In this study, screening by LC–MS and cytotoxicity-guided isolation led to the identification of ulleungamide C (1), a previously unknown pipecolic acid-rich branched cyclic depsipeptide, from a soil actinobacterium Streptomyces sp. KCB13F003. The structure of 1 was determined by interpretation of spectroscopic and spectrometric data from 1D and 2D NMR and HRESIMS experiments. Antiproliferative assays using mammalian cancerous cells revealed that 1 inhibits the proliferation of HL-60 human promyelocytic leukemia cells. Cell cycle analysis showed an increased accumulation of cells in the G0/G1 phase after treatment with 1. Results of immunoblotting assays revealed that 1 reduced the expression levels of cyclin-dependent kinase 4 (CDK4), CDK6, retinoblastoma protein (Rb), and phosphorylated Rb, whereas it induced cyclin-dependent kinase inhibitor 1B (p27/Kip1) expression.



中文翻译:

来自链霉菌属物种的富含哌可酸的支链环缩酚酰胺 C 诱导早幼粒细胞白血病细胞的 G0/G1 细胞周期停滞

在这项研究中,通过 LC-MS 筛选和细胞毒性引导分离导致从土壤放线菌Streptomyces sp. 中鉴定出 ulleungamide C ( 1 ),这是一种以前未知的富含哌啶酸的支链环缩肽。KCB13F003。1的结构是通过对来自 1D 和 2D NMR 和 HRESIMS 实验的光谱和光谱数据的解释来确定的。使用哺乳动物癌细胞进行的抗增殖试验表明1抑制 HL-60 人早幼粒细胞白血病细胞的增殖。细胞周期分析显示在用1处理后 G0/G1 期细胞的积累增加。免疫印迹分析结果显示,1 降低细胞周期蛋白依赖性激酶 4 (CDK4)、CDK6、成视网膜细胞瘤蛋白 (Rb) 和磷酸化 Rb 的表达水平,而它诱导细胞周期蛋白依赖性激酶抑制剂 1B (p27/Kip1) 表达。

更新日期:2020-11-18
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