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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

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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.

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Acknowledgments

This study was supported by Grants (2010-0003064 and 2012R1A1A2039477) of the Basic Science Research Prcogram through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology, South Korea.

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Authors and Affiliations

  1. Department of Life Science, College of Natural Sciences, Ewha Womans University, Seoul, 120-750, South Korea

    Hwa-Kyung Kim & Dong-Hoon Hyun

  2. Research Center, Dongnam Institute of Radiological and Medical Science, Busan, 619-953, South Korea

    Tae Gen Son

  3. School of Pharmacy, Sungkyunkwan University, Suwon, 440-746, South Korea

    Dong-Gyu Jo

  4. Department of Intergrated Materials Engineering, Chungwoon University, Incheon, 402-803, South Korea

    Dong Chung Kim

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Kim, HK., Son, T.G., Jo, DG. et al. 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. Arch. Pharm. Res. 39, 1339–1348 (2016). https://doi.org/10.1007/s12272-016-0817-6

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