Ursolic acid triggers apoptosis in human osteosarcoma cells via caspase activation and the ERK1/2 MAPK pathway.
J Agric Food Chem. 2016 May 12. Epub 2016 May 12. PMID: 27171502
Ursolic acid (UA), a naturally occurring pentacyclic triterpene acid found in many medicinal herbs and edible plants, has been shown to trigger apoptosis in several lines of tumor cells in vitro. We found that treatment with UA suppressed the viability of human osteosarcoma MG-63 cells and induced cell cycle arrest at sub-G1 and G2/M phases. Furthermore, exposure to UA induced intracellular oxidative stress and collapse of mitochondrial membrane permeability, resulting in the subsequent activation of apoptotic caspases 8, 9 and 3 as well as PARP cleavage, ultimately to apoptosis in MG-63 cells. Moreover, protein analysis of MAPK-related protein expression showed an increase in activated ERK1/2, JNK, and p38 MAPK in UA-treated MG-63 cells. In addition, UA-induced apoptosis was significantly abolished in MG-63 cells that had been pre-treated with inhibitors of caspase 3, 8 and 9 and ERK1/2. Furthermore, UA-treated MG-63 cells also exhibited an enhancement in Bax/Bcl-2 ratio whereas anti-apoptotic XIAP and survivin were downregulated. Taken together, we provide evidence demonstrating that ursolic acid mediates caspase-dependant and ERK1/2 MAPK-associated apoptosis in osteosarcoma MG-63 cells. Key words: ursolic acid, MG-63 cells, apoptosis, MAPK, caspase.