Τίτλος:
The dietary triterpenoid 18α–Glycyrrhetinic acid protects from MMC-induced genotoxicity through the ERK/Nrf2 pathway
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
18α–Glycyrrhetinic acid (18α-GA) is a bioactive triterpenoid that has been shown to activate the nuclear factor (erythroid-derived-2)-like 2 (Nrf2), the main transcription factor that orchestrates the cellular antioxidant response, in both cellular and organismal context. Although various beneficial properties of 18α-GA have been revealed, including its anti-oxidation and anti-aging activity, its possible protective effect against DNA damage has never been addressed. In this study, we investigated the potential beneficial properties of 18α-GA against DNA damage induced by mitomycin C (MMC) treatment. Using human primary fibroblasts exposed to MMC following pre-treatment with 18α-GA, we reveal an Nrf2-mediated protective effect against MMC-induced cell death that depends on extracellular signal–regulated kinase (ERK) signaling. In total, our results reveal an additional beneficial effect of the Nrf2 activator 18α-GA, suggesting that this important phytochemical compound is a potential candidate in preventive and/or therapeutic schemes against conditions (such as aging) or diseases that are characterized by both oxidative stress and DNA damage. © 2019
Συγγραφείς:
Lefaki, M.
Papaevgeniou, N.
Tur, J.A.
Vorgias, C.E.
Sykiotis, G.P.
Chondrogianni, N.
Λέξεις-κλειδιά:
18alpha glycyrrhetinic acid; mitogen activated protein kinase; mitomycin; transcription factor Nrf2; 18alpha-glycyrrhetinic acid; glycyrrhetinic acid; mitomycin; NFE2L2 protein, human; reactive oxygen metabolite; transcription factor Nrf2, antioxidant activity; Article; cell death; cell protection; cell survival; controlled study; DNA damage; drug effect; drug mechanism; embryo; enzyme activation; fibroblast; gene targeting; genotoxicity; human; human cell; MAPK signaling; oxidative stress; priority journal; protein expression; protein phosphorylation; treatment outcome; upregulation; apoptosis; cell line; cytology; gene expression regulation; genetics; MAPK signaling; metabolism, Apoptosis; Cell Line; DNA Damage; Fibroblasts; Gene Expression Regulation; Glycyrrhetinic Acid; Humans; MAP Kinase Signaling System; Mitomycin; NF-E2-Related Factor 2; Oxidative Stress; Reactive Oxygen Species
DOI:
10.1016/j.redox.2019.101317
