Inhibition of cancer cell growth by oleanolic acid in multidrug resistant liver carcinoma is mediated via suppression of cancer cell migration and invasion, mitochondrial apoptosis, G2/M cell cycle arrest and deactivation of JNK/p38 signalling pathway.
J BUON. 2019 Sep-Oct;24(5):1964-1969. PMID: 31786862
PURPOSE: Liver cancer accounts for considerable mortality across the globe. The sharp upsurge in the incidence of liver cancer, unavailability of standard treatments and the adverse side effects associated with the existing drugs has made it compulsory to explore novel and more effective anticancer molecules. In this study the anticancer effects of a natural compound oleanolic acid were investigated in vitro.
METHODS: The human HepG2 liver cancer cells were treated with various concentrations of oleanolic acid for 24 h. The antiproliferative effects of oleanolic acid were measured by CCK8 cell viability assay. DAPI and annexin V/propidium iodide (PI) assays were employed to examine the induction of apoptosis. Transwell assay was performed to examine the cell migration and invasion. Expression analysis was performed by western blot analysis.
RESULTS: The results showed that oleanolic acid decreased the viability of the liver cancer HepG2 cells and exhibited an IC50 of 30µM. The cytotoxicity of oleanolic acid was also investigated on the normal liver cells AML12 and it was found that oleanolic acid and exerted very low toxic effects on these cells and exhibited an IC50 of 120 µM. Oleanolic acid also caused remarkable changes in the morphology of the HepG2 cells and inhibited their colony formation potential. Flow cytometry indicated oleanolic acid triggered G2/M arrest of the liver HepG2 cancer cells. PI and DAPI staining revealed that oleanolic acid prompted apoptosis of the HepG2 cells. The apoptotic cells increased from 2.2% in control to around 35% at 30µM concentration. Oleanolic acid also suppressed the migration and invasion of the liver cancer cells via blocking of the JNK/p38 signalling pathway.
CONCLUSIONS: The results of the current research revealed that oleanolic acid can be a molecule that may be utilised in the treatment of liver cancer in the future.