Background
Statins can reduce the malignancies through stimulating apoptosis. We aimed to elucidate the role of lovastatin in HepG-2 cells.
Conclusions
Lovastatin significantly induced cell apoptosis by activating ROS-dependent mitochondrial and ER stress pathways in HepG-2 cells.
Methods
HepG-2 and non-tumor L-O2 cells were used as the cell models. CCK-8, flow cytometric analysis and carboxy fluorescein diacetate succinimidyl ester (CFDA-SE) labeling were performed to monitor the viability, apoptosis and proliferation.
Results
We found that lovastatin exerted the most tumor suppressing effects on liver cancer cells among the three tested statins. Lovastatin treatment significantly reduced cell viability and proliferation, and induced apoptosis in HepG-2. However, drug resistance effects were observed in the non-tumor L-O2 cells. The apoptosis triggered by lovastatin was accompanied by high intracellular levels of ROS. Pretreatment with the ROS blocker N-acetyl-cysteine (NAC) could mitigate the lovastatin-induced cytotoxicity in HepG-2 cells. Mechanistically, lovastatin increased HepG-2 cell apoptosis by triggering mitochondrial and endoplasmic reticulum (ER) stress pathways through ROS accumulation. Conclusions: Lovastatin significantly induced cell apoptosis by activating ROS-dependent mitochondrial and ER stress pathways in HepG-2 cells.