title: Paradoxical cellular effects and biological role of the multifaceted compound nordihydroguaiaretic acid.
abstract: Nordihydroguaiaretic acid (NDGA) is a phenolic compound obtained from the leaves of the evergreen desert shrub Larrea tridentata (Creosote bush), which has been used anciently in folk medicine for the treatment of multiple diseases. At the molecular level, NDGA is a potent scavenger of reactive oxygen species. Lipoxygenase inhibition by NDGA has been broadly studied over several cell models; however, NDGA exerts other antioxidant properties and cytoprotective effects in non-tumor cells, which are related with its role as modulator of the nuclear factor erythroid 2-related factor 2 (Nrf2)/antioxidant response element (ARE) antioxidant pathway. In contrast, in tumor cells NDGA exerts pro-apoptotic activity and anti-tumor effects. Different effects of NDGA have been observed in mitochondria, where NDGA prevents mitochondrial damage in non-tumor cells and induces loss of mitochondrial function in tumor cells. Moreover, NDGA exerts beneficial effects in diverse diseases like cancer, renal damage, Huntington's disease, Alzheimer's disease, and other neurodegenerative pathologies. This work represents a critical review about relevant NDGA mechanisms, cellular effects, and signal pathways involved with possible useful effects.
authors.affiliation: Faculty of Chemistry, Department of Biology, National Autonomous University of Mexico (UNAM), University City, D.F., Mexico.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Hernández-Damián
authors.forename: Ana Cristina
authors.initials: AC
authors.lastname: Andérica-Romero
authors.forename: José
authors.initials: J
authors.lastname: Pedraza-Chaverri
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D061745:Antioxidant Response Elements / Q000187:drug effects; D015195:Drug Design; D016166:Free Radical Scavengers / Q000737:chemistry / Q000494:pharmacology*; D005786:Gene Expression Regulation; D006801:Humans; D016859:Lipoxygenase Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D009637:Masoprocol / Q000737:chemistry / Q000494:pharmacology*; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D015394:Molecular Structure; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D018696:Neuroprotective Agents / Q000737:chemistry / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D016166:Free Radical Scavengers; D016859:Lipoxygenase Inhibitors; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; D018696:Neuroprotective Agents; D017382:Reactive Oxygen Species; D009637:Masoprocol
keywords: Antioxidant; Antitumoral activity; Nordihydroguaiaretic acid; Nrf2; Reactive oxygen species