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金钱松中环阿尔廷-贝壳杉烷异二聚体通过细胞周期阻滞和诱导凋亡抑制HL-60细胞生长。

Inhibition of HL-60 cell growth via cell cycle arrest and apoptosis induction by a cycloartane-labdane heterodimer from Pseudolarix amabilis.

作者信息

Tian Xinhui, Yang Niao, Li Bo, Zhang Jianping, Xu Xike, Yue Rongcai, Li Huiliang, Chen Liping, Shen Yunheng, Zhang Weidong

机构信息

Department of Phytochemistry, School of Pharmacy, Second Military Medical University, Shanghai 200433, P. R. China.

Innovative Research Center of Traditional Chinese Medicine, Shanghai Institute of Pharmaceutical Industry, Shanghai 201204, P. R. China.

出版信息

Org Biomol Chem. 2016 Mar 7;14(9):2618-24. doi: 10.1039/c5ob02661j.

Abstract

Pseudolaridimer C (), a rarely encountered cycloartane-labdane Diels-Alder adduct was isolated from the cones of Pseudolarix amabilis. The structure and absolute configuration of were established by comprehensive NMR and CD spectral analysis. The WST-8 assay indicated that time and dose dependently inhibited the proliferation of human leukemia cells HL-60 at 1-10 μM. DAPI and Annexin V-FITC/PI double staining method, and DNA ladder experiments all proved that had significant dose-dependent effects on HL-60 cell apoptosis. A further mechanism study indicated that the apoptosis was associated with the cell cycle arrest during the G2/M phase, and the activation of caspase-9, -3, -7, and poly-(ADP-ribose)-polymerase (PARP).

摘要

伪海松二聚体C()是从美丽异叶松球果中分离得到的一种罕见的环阿尔廷烷-半日花烷狄尔斯-阿尔德加合物。通过全面的核磁共振和圆二色谱光谱分析确定了其结构和绝对构型。WST-8检测表明,在1-10μM浓度下,其对人白血病细胞HL-60的增殖具有时间和剂量依赖性抑制作用。DAPI和膜联蛋白V-FITC/PI双染色法以及DNA梯状实验均证明其对HL-60细胞凋亡具有显著的剂量依赖性作用。进一步的机制研究表明,细胞凋亡与G2/M期的细胞周期阻滞以及半胱天冬酶-9、-3、-7和聚(ADP-核糖)聚合酶(PARP)的激活有关。

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