Effects of Erythrodiol on the Antioxidant Response and Proteome of HepG2 Cells

Abstract

Erythrodiol (EO) is a pentacyclic triterpenic alcohol found in olive tree leaves and olive oil, and it has important effects on the health properties and quality of olive oil. In this study, we characterized the cytotoxic effects of EO on human hepatocarcinoma (HepG2) cells by studying changes in cell viability, reactive oxygen species (ROS) production, antioxidant defense systems, and the proteome. The results reveal that EO markedly decreased HepG2 cell viability without changing ROS levels. The concentrations of glutathione and NADPH were significantly reduced, with selective changes in the activity of several antioxidant enzymes: glutathione peroxidase, glutathione reductase, glucose 6-phosphate dehydrogenase, and 6-phosphogluconate dehydrogenase. Proteomic data reveal that EO led to the complete elimination or decreased abundance of 41 and 3 proteins, respectively, and the abundance of 29 proteins increased. The results of functional enrichment analysis show that important metabolic processes and the nuclear transport of mature mRNA were impaired, whereas AMP biosynthesis and cell cycle G2/M phase transition were induced. The transcription factors and miRNAs involved in this response were also identified. These potent antiproliferative effects make EO a good candidate for the further analysis of its hepatic antitumor effects in in vivo studies.

Artemisia arborescens and Artemisia inculta from Crete; Secondary Metabolites, Trace Metals and In Vitro Antioxidant Activities

“…Additionally, ursolic acid isolated from the methanolic extracts of A. capillaris inhibited the growth of both susceptible and resistant strains of Mycobacterium tuberculosis, exhibiting promising results against tuberculosis [ 42 ]. It is noteworthy that erythrodiol and uvaol, well-known for their antioxidant and anti-inflammatory activities [ 43 , 44 ], were identified only in the aqueous-glycerol extracts. To the best of our knowledge, this is the first time these two terpenoids are identified in an Artemisia extract.…”

Nutraceutical Role of Polyphenols and Triterpenes Present in the Extracts of Fruits and Leaves of Olea europaea as Antioxidants, Anti-Infectives and Anticancer Agents on Healthy Growth

“…In addition, in a recent study, the antioxidant and antitumor capacity of erythrodiol (EO) was demonstrated in HepG2 liver carcinoma cells [ 113 ]. The results show that EO reduced the viability of HepG2 cells without changing ROS levels, whereas glutathione reduced (GSH) and NADPH levels were reduced, with selective changes in the activity of several antioxidant enzymes, catalase (CAT), superoxide dismutase (SOD), glutathione S -transferase (GST), glutathione peroxidase (GPX), glutathione reductase (GR), glucose 6-phosphate dehydrogenase (G6PDG), and 6-phosphogluconate dehydrogenase (6PGDH).…”

“…The results show that EO reduced the viability of HepG2 cells without changing ROS levels, whereas glutathione reduced (GSH) and NADPH levels were reduced, with selective changes in the activity of several antioxidant enzymes, catalase (CAT), superoxide dismutase (SOD), glutathione S -transferase (GST), glutathione peroxidase (GPX), glutathione reductase (GR), glucose 6-phosphate dehydrogenase (G6PDG), and 6-phosphogluconate dehydrogenase (6PGDH). Furthermore, EO was able to significantly modify the proteome of these cells, revealing that nuclear transport of mature mRNA was significantly reduced, while AMP biosynthesis and the G 2 /M phase transition of the cell cycle were induced, thus demonstrating its high anticancer potency [ 113 ].…”