Induction of apoptosis by Oleracein A and Oleracein B in HepG2 cancerous cells is mediated by ceramide generation, caspase-9/caspase-3 pathway activation, and oxidative damage

Abstract

The present study aimed to discover whether oleracein A (OA) and oleracein B (OB) have anti-proliferative effects on HepG2 cell line and, if so, by which mechanisms they exert their effects. The results demonstrate that both OA and OB are independently able to decrease the viability of HepG2 cells in a concentration-dependent manner. The levels of ceramide in HepG2 cells, however, were increased after treatment with both OA and OB, a phenomenon further confirmed by the alteration of the post-treatment activity of some ceramide-related enzymes, including acid ceramidase (aCDase), neutral sphingomyelinase (SMase), and glucosylceramide synthase (GCS). Moreover, the cellular redox status of oleracein-treated HepG2 cells was evaluated by measuring the activity of some antioxidant enzymes, including catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPX). The activity of the mentioned enzymes was reduced in the presence of OA and OB, leading to oxidative damage. The caspase-9/caspase-3 pathway was also activated in oleracein-treated HepG2 cells. The overall results suggest that ceramide generation, oxidative damage, and caspase activation are the mechanisms of action of apoptosis induction in oleracein-treated HepG2 cells.

Keywords

• Oleracein A
• Oleracein B
• Chemoprevention
• Ceramide
• Caspase-9/caspase-3 pathway
• Oxidative damage