eudesmanolide and Liver-Neoplasms

Fractionation of the ethanol extract of Artemisia verlotorum led to the identification of eight undescribed eudesmane-type sesquiterpenoids, artemverlolides A-H (1-8). Their structures were determined by spectral analyses (HRESIMS, 1D and 2D NMR, IR, and ECD). Network pharmacology predicted that compounds 1-8 might be target on AURKA, CCNA2, CYP2C19, and EPHX2 with possibly antihepatoma effect from Swiss TargetPrediction and Gene Expression Omnibus database. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses showed that the targets significantly enriched in FoxO signaling pathway. The molecular docking suggested that compound 8 had high binding affinity with AURKA. Furthermore, the interaction between compound 8 and AURKA was determined by Surface Plasmon Resonance (SPR) assay. The result suggested that compound 8 bound to AURKA with KD value of 68.0μM and was consistent with the predicted data, demonstrating that AURKA might be one of acting targets of 8.

Topics: Artemisia; Aurora Kinase A; Carcinoma, Hepatocellular; Drugs, Chinese Herbal; Liver Neoplasms; Molecular Docking Simulation; Molecular Structure; Network Pharmacology

Telekin, isolated from the Chinese herb Carpesium divaricatum, has shown anti-proliferation effects against various cancer cells, including hepatocellular carcinoma cells. In this study, we investigated the anti-proliferation mechanisms of telekin in human hepatocellular carcinoma HepG2 cells in vitro.. HepG2 cells were treated with telekin. Cell viability was evaluated using MTT assay. Flow cytometry was used to measure cell cycle profiles, ROS level and apoptosis. The protein expression levels were analyzed with Western blotting.. Telekin (3.75-30 μmol/L) dose-dependently inhibited the viability of HepG2 cells and induced l apoptosis. Furthermore, the treatment induced cell cycle arrest at G2/M phase, accompanied by significantly increased the phosphorylation of Cdc25A and Cdc2, and decreased Cyclin B1 level. Moreover, the treatment significantly stimulated ROS production, and increased the phosphorylation of p38 and MAPKAPK-2 in the cells. Pretreatment with the antioxidant NAC (2.5, 5, and 10 mmol/L), or the p38 MAPK inhibitor SB203580 (2.5 and 5 μmol/L) dose-dependently attenuated these telekin-induced effects in the cells.. Telekin suppresses hepatocellular carcinoma cells in vitro by inducing G2/M phase arrest via activating the p38 MAPK pathway.

Topics: Apoptosis; Carcinoma, Hepatocellular; CDC2 Protein Kinase; cdc25 Phosphatases; Cell Cycle Checkpoints; Cell Line, Tumor; Cell Proliferation; Cell Survival; Cyclin B1; Cyclin-Dependent Kinases; G2 Phase Cell Cycle Checkpoints; Hep G2 Cells; Humans; Intracellular Signaling Peptides and Proteins; Liver Neoplasms; p38 Mitogen-Activated Protein Kinases; Protein Serine-Threonine Kinases; Reactive Oxygen Species; Sesquiterpenes, Eudesmane; Signal Transduction