title: Cytotoxicity of lipid-soluble ginseng extracts is attenuated by plasma membrane redox enzyme NQO1 through maintaining redox homeostasis and delaying apoptosis in human neuroblastoma cells.
abstract: Lipid-soluble ginseng extracts (LSGE) is known to inhibit many types of cancer cells through arresting cell cycle and inducing apoptosis. Usually, normal cells are can also be damaged by anti-tumor reagents. The plasma membrane redox system (PMRS) is enhanced to compensate mitochondrial dysfunction and impaired energy metabolism. NADH-quinone oxidoreductase 1 (NQO1), a plasma membrane redox enzyme, is known to be induced by panaxytriol, one of components of lipid-soluble ginseng extracts (LSGE). The objective of this study was determine the mechanisms of NQO1 involved in neuroprotection in response to cytotoxicity induced by LSGE. Exposure of control SH-SY5Y cells to LSGE resulted in dramatic loss of cell viability in a dose-dependent manner. The loss of cell viability was significantly recovered in cells transfected with NQO1. LSGE-induced cell death occurred through apoptosis such as cell shrinkage, chromatin condensation and cleavage of poly (ADP-ribose) polymerase. These apoptotic features were significantly attenuated by overexpression of NQO1. Levels of oxidative/nitrative damage were highly elevated by LSGE in a dose-dependent manner. However, these elevated levels were greatly reduced by overexpression of NQO1. In addition, overexpression of NQO1 attenuated the decrease in mitochondrial complex I activity caused by LSGE. Taken together, these findings suggest that overexpressed NQO1 can protect cells against LSGE-induced cytotoxicity through lowering oxidative/nitrative damage and delaying apoptosis, supporting that stimulation of NQO1 activity could be a therapeutic targets in neurodegeration.
authors.affiliation: Department of Life Science, College of Natural Sciences, Ewha Womans University, Seoul, 120-750, South Korea.
authors.forename: Hwa-Kyung
authors.initials: HK
authors.lastname: Kim
authors.affiliation: Research Center, Dongnam Institute of Radiological and Medical Science, Busan, 619-953, South Korea.
authors.forename: Tae Gen
authors.initials: TG
authors.lastname: Son
authors.affiliation: School of Pharmacy, Sungkyunkwan University, Suwon, 440-746, South Korea.
authors.forename: Dong-Gyu
authors.initials: DG
authors.lastname: Jo
authors.affiliation: Department of Intergrated Materials Engineering, Chungwoon University, Incheon, 402-803, South Korea.
authors.forename: Dong Chung
authors.initials: DC
authors.lastname: Kim
authors.affiliation: Department of Life Science, College of Natural Sciences, Ewha Womans University, Seoul, 120-750, South Korea. hyundh@ewha.ac.kr.
authors.forename: Dong-Hoon
authors.initials: DH
authors.lastname: Hyun
mesh_terms: D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000187:drug effects / Q000201:enzymology*; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D003603:Cytotoxins / Q000302:isolation & purification / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D004790:Enzyme Induction / Q000187:drug effects / Q000502:physiology; D006706:Homeostasis / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D008055:Lipids; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000096:biosynthesis*; D009447:Neuroblastoma / Q000201:enzymology*; D010084:Oxidation-Reduction / Q000187:drug effects; D005894:Panax; D010936:Plant Extracts / Q000302:isolation & purification / Q000633:toxicity*; D012995:Solubility
chemical_list: D003603:Cytotoxins; D008055:Lipids; D010936:Plant Extracts; D016660:NAD(P)H Dehydrogenase (Quinone); C447479:NQO1 protein, human
keywords: Apoptosis; Lipid-soluble ginseng extracts; NQO1; Oxidative damage; PMRS