ABSTRACT
Natural products have a significant role in the development of new drugs, being relevant the pentacyclic triterpenes extracted from Olea europaea L. Anticancer effect of uvaol, a natural triterpene, has been scarcely studied. The aim of this study was to understand the anticancer mechanism of uvaol in the HepG2 cell line. Cytotoxicity results showed a selectivity effect of uvaol with higher influence in HepG2 than WRL68 cells used as control. Our results show that uvaol has a clear and selective anticancer activity in HepG2 cells supported by a significant anti-migratory capacity and a significant increase in the expression of HSP-60. Furthermore, the administration of this triterpene induces cell arrest in the G0/G1 phase, as well as an increase in the rate of cell apoptosis. These results are supported by a decrease in the expression of the anti-apoptotic protein Bcl2, an increase in the expression of the pro-apoptotic protein Bax, together with a down-regulation of the AKT/PI3K signaling pathway. A reduction in reactive oxygen species (ROS) levels in HepG2 cells was also observed. Altogether, results showed anti-proliferative and pro-apoptotic effect of uvaol on hepatocellular carcinoma, constituting an interesting challenge in the development of new treatments against this type of cancer.
Subject(s)
Apoptosis/drug effects , Cell Proliferation/drug effects , G1 Phase Cell Cycle Checkpoints/drug effects , Reactive Oxygen Species/metabolism , Signal Transduction/drug effects , Triterpenes/pharmacology , Carcinoma, Hepatocellular/metabolism , Carcinoma, Hepatocellular/pathology , Cell Movement/drug effects , Cell Survival/drug effects , Hep G2 Cells , Humans , Liver Neoplasms/metabolism , Liver Neoplasms/pathology , Olea/chemistry , Olea/metabolism , Oxidative Stress/drug effects , Phosphatidylinositol 3-Kinases/metabolism , Plant Extracts/chemistry , Proto-Oncogene Proteins c-akt/metabolism , Triterpenes/chemistryABSTRACT
Objective To investigate the effect of sodium demethylcantharidate injection on adherence,invasion and metastasis and to investigate the related mechanism in human hepatocarcinoma cell line HepG2.Methods Adherence ability,migration and invasion of HepG2 cells inhibited by sodium demethylcantharidate injection were assessed by MTT and Transwell techniques.Expression levels of MMP-9 protein in HepG2 cells were determined by immunohistochemistry.Results The number of adhesion,migration and invasion of HepG2 cells were significantly lower in sodium demethylcantharidate injection group than those in the control group (P ＜ 0.05).HepG2 cells co-incubated with sodium demethylcantharidate injection in the concentration of 0.25 μg/ml for 30,60,90 and 120 min showed higher cell adhesion than the control group.The adhesion inhibition ratios were 48.11％,33.81％,28.97 ％ and 16.83 ％,respectively.The migration and invasion inhibition rates were 64.19 ％ and 58.19 ％.With concentration of sodium demethylcantharidate injection to increasing,expression levels of MMP-9 protein in HepG2 cells more and more lower than control group.Conclusion The adherence,migration and invasion abilities of HepG2 cells are markedly inhibited by sodium demethylcantharidate injection,the mechanisms is possible related to the expression levels of MMP-9 protein.
