中国金钱菊中的倍半萜类化合物对肝细胞癌细胞触发了ROS诱导的凋亡和保护性自噬。
Sesquiterpenes from Carpesium faberi triggered ROS-induced apoptosis and protective autophagy in hepatocellular carcinoma cells.
发表日期：2023 Jul 30
作者：
Ying Yan, Jie Chen, Mingyou Peng, Xiong Zhang, Enming Feng, Qingdan Li, Bing Guo, Xiao Ding, Yu Zhang, Lei Tang
来源：
PHYTOCHEMISTRY
摘要：
从金鸡菊的整株植物中分离得到了十个前所未见的倍半萜化合物，命名为Carpespenes A-J (1-10)，以及八个已知化合物 (11-18)。通过高分辨质谱、核磁共振和电子环状二色谱的广泛分析，确定了它们的结构。其中Carpespene A (1) 是一种含有开环五元环的欧德三烯型倍半萜内酯。此外，化合物1 对四种癌细胞株表现出明显的细胞毒性作用，IC50值分别为8.20至18.45 μM，与阳性对照顺铂和多柔比星相比。机制上，化合物1通过引发过量的ROS积累诱导了HepG2细胞的凋亡。然而后者诱导了细胞保护性的自噬作用，从而削弱了化合物1的细胞毒性。采用化合物1处理同时抑制自噬的方法，可以增强其对HepG2细胞的细胞毒性作用。我们的研究结果进一步揭示了倍半萜的结构多样性和生物活性，并为以细胞保护性自噬为靶点的潜在化疗策略提供了实验依据。版权所有 © 2023 Elsevier Ltd. 发表
Ten previously undescribed sesquiterpenes, carpespenes A-J (1-10), and eight known compounds (11-18), were isolated from the whole plants of Carpesium faberi. Their structures were established by extensive analysis of HRESIMS, NMR, and ECD spectra. Carpespene A (1) is eudesmanolide-type sesquiterpene lactone with an open five membered ring involving C-2 and C-3. Furthermore, compound 1 showed significant cytotoxic effects against four cancer cell lines with IC50 values from 8.20 to 18.45 μM, compared with the positive controls cisplatin and doxorubicin. Mechanistically, compound 1 induced apoptosis in the HepG2 cells by triggering excessive ROS accumulation. The latter however induced cytoprotective autophagy, which impaired the cytotoxicity of compound 1. Simultaneous antophagy inhibition with compound 1 treatment augmented the cytotoxic effects of the latter on HepG2 cells. Our findings further establish the structural diversity and bioactivity of sesquiterpenes, and provide an experimental basis for targeting cytoprotective autophagy as a potential chemotherapeutic strategy.Copyright © 2023. Published by Elsevier Ltd.