Abstract

Fourteen sesquiterpene lactones were isolated from the whole plant of Carpesium abrotanoides L. Their structures were determined on the basis of comprehensive spectroscopic data analysis. All compounds were screened for their cytotoxic activity, and compound 6 showed the strongest activity (IC₅₀ 2.73 − 7.21 µM) against five human cancer cell lines, including A549, HepG2, HCT116, MDA-MB-231, and CNE2. Compound 6 was further investigated. Compound 6 effectively induced G2/M cell cycle arrest and ROS accumulation in a dose-dependent manner, which further led to apoptosis in cancer cells. Interestingly, compounds 1 and 6 could also activate protective autophagy, which was reported for the first time in sesquiterpene isolated from Carpesium abrotanoides. In addition, compounds 1 and 6 could induce lysosomal biogenesis by 173.2% and 163.7%, respectively. In sum, sesquiterpene lactones from Carpesium abrotanoides could induce apoptosis and protective autophagy in cancer cells, which provide a serial of compounds with potential clinical applications.

摘要

从Carpesium abrotanoides L的全株中分离得到14个倍半萜内酯。它们的结构是在综合光谱数据分析的基础上确定的。筛选了所有化合物的细胞毒活性，化合物6对五种人类癌细胞系（包括 A549、HepG2、HCT116、MDA-MB-231 和 CNE2）显示出最强的活性 (IC _{50 2.73 - 7.21 µM)。}进一步研究了化合物6 。化合物6以剂量依赖性方式有效诱导 G2/M 细胞周期停滞和 ROS 积累，这进一步导致癌细胞凋亡。有趣的是，化合物1和6还可以激活保护性自噬，这在从Carpesium abrotanoides中分离出的倍半萜中首次被报道。此外，化合物1和6可分别诱导 173.2% 和 163.7% 的溶酶体生物发生。综上所述，Carpesium abrotanoides中的倍半萜内酯可诱导癌细胞凋亡和保护性自噬，为一系列具有潜在临床应用价值的化合物提供了可能。