2. Academic Validation
  3. Elephantopinolide A-P, germacrane-type sesquiterpene lactones from Elephantopus scaber induce apoptosis, autophagy and G2/M phase arrest in hepatocellular carcinoma cells

Elephantopinolide A-P, germacrane-type sesquiterpene lactones from Elephantopus scaber induce apoptosis, autophagy and G2/M phase arrest in hepatocellular carcinoma cells

  • Eur J Med Chem. 2020 Jul 15:198:112362. doi: 10.1016/j.ejmech.2020.112362.
Ming Bai 1,  Jing-Jie Chen 1,  Wei Xu 1,  Shu-Hui Dong 1,  Qing-Bo Liu 1,  Bin Lin 2,  Xiao-Xiao Huang 3,  Guo-Dong Yao 4,  Shao-Jiang Song 5
Affiliations

Affiliations

  • 1 Key Laboratory of Computational Chemistry Based Natural Antitumor Drug Research & Development, Liaoning Province, School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang, 110016, People's Republic of China.
  • 2 School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang, 110016, People's Republic of China.
  • 3 Key Laboratory of Computational Chemistry Based Natural Antitumor Drug Research & Development, Liaoning Province, School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang, 110016, People's Republic of China. Electronic address: xiaoxiao270@163.com.
  • 4 Key Laboratory of Computational Chemistry Based Natural Antitumor Drug Research & Development, Liaoning Province, School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang, 110016, People's Republic of China. Electronic address: guodong_yao@126.com.
  • 5 Key Laboratory of Computational Chemistry Based Natural Antitumor Drug Research & Development, Liaoning Province, School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang, 110016, People's Republic of China. Electronic address: songsj99@163.com.
PMID: 32371334 DOI: 10.1016/j.ejmech.2020.112362
Abstract

Chromatographic purification of Elephantopus scaber led to 16 new germacrane-type sesquiterpene lactones (1-16), named elephantopinolide A-P, along with a known analogue (17). Their structures were confirmed by comprehensive spectroscopic analyses, single-crystal X-ray diffraction, and comparison between the experimental and calculated ECD spectra. Their hepatocellular inhibition activities against Hep3B and HepG2 cells were screened by MTT assay, and the structure-activity relationships were examined. The results revealed that 10 (IC50 value of 2.83 μM and 1.98 μM) is more potent than sorafenib. The underlying mechanism study demonstrated that 10 could markedly induce Apoptosis accompanied by increased ROS production and decreased mitochondrial membrane potential, resulting in the Autophagy and G2/M phase cell arrest in Hep3B and HepG2 cells. Furthermore, signal pathways including MAPKs and Akt may play important roles in 10-induced hepatocellular carcinoma cells death.

Keywords

Anti-hepatocarcinoma effect; Apoptosis; Elephantopus scaber; Germacrane-type sesquiterpene lactones.

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