从矮山矾中提取的Meroterpenoids通过抑制A549细胞中的PI3K/Akt/mTOR信号通路,在体外显示出具有潜在抗肿瘤活性。
Meroterpenoids from Daphne genkwa shows promising in vitro antitumor activity via inhibiting PI3K/Akt/mTOR signaling pathway in A549 cells.
发表日期:2023 Aug 23
作者:
Ren-Fen Ma, Hu Liu, Xue-Chun Zhao, Peipei Shan, Ping Sun, Jun-Juan Xue, Guodong Wei, Hua Zhang
来源:
BIOORGANIC CHEMISTRY
摘要:
对秧王花(Daphne genkwa)的叶片和枝干进行了植物化学研究,共得到25个萜类二次代谢物(1-16),其中包括9对对映异构体(1a/1b-8a/8b和12a/12b),其中有20个化合物首次在本研究中报道。通过全面的光谱分析,特别是电子圆二色性(ECD)和莫舍尔方法,确定了新化合物(不包括10-13)的结构和绝对构型。初步的体外细胞存活率实验显示,选择性化合物对A549(肺癌)、Hela(宫颈癌)、MDA-MB231(乳腺癌)和MCF-7(乳腺癌)癌细胞具有显著的细胞毒性,其中化合物8a对这四个细胞株的IC50值在3.12-4.67μM范围内,表现出最佳的抑制活性。进一步的体外抗肿瘤评估表明,8a能够抑制A549细胞的增殖和转移,并诱导明显的凋亡和细胞周期停滞。进一步的机制研究发现,8a能够通过抑制PI3K/Akt/mTOR信号通路发挥其抗肿瘤活性。版权所有 © 2023 Elsevier Inc. 保留所有权利。
Phytochemical investigation into the leaves and branches of Daphne genkwa afforded 25 meroterpenoids (1-16) including nine pairs of enantiomers (1a/1b-8a/8b and 12a/12b), among which 20 compounds have been reported in the present work for the first time. The structures with absolute configurations of the new molecules (excluding 10-13) were established via comprehensive spectroscopic analyses especially electronic circular dichroism (ECD) and Mosher's methods. A preliminary in vitro cell viability assay revealed remarkable cytotoxicities of selective compounds against A549 (lung), Hela (cervical), MDA-MB231 (breast) and MCF-7 (breast) cancer cells, and compound 8a showed the best inhibitory activity with IC50 values in the range of 3.12-4.67 μM toward the four cell lines. Subsequent in vitro antitumor evaluation of 8a disclosed that it could inhibit the proliferation and metastasis, as well as induce significant apoptosis and cycle arrest, of A549 cells. Further mechanistic investigations revealed that 8a could exert its antitumor activity via inhibiting the PI3K/Akt/mTOR signaling pathway.Copyright © 2023 Elsevier Inc. All rights reserved.