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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- 作者：Hwa-Kyung Kim ; Tae Gen Son ; Dong-Gyu Jo ; Dong Chung Kim…
- 关键词：Lipid ; soluble ginseng extracts ; NQO1 ; PMRS ; Oxidative damage ; Apoptosis
- 刊名：Archives of Pharmacal Research
- 出版年：2016
- 出版时间：October 2016
- 年：2016
- 卷：39
- 期：10
- 页码：1339-1348
- 全文大小：1,716 KB
- 刊物主题：Pharmacy; Pharmacology/Toxicology;
- 出版者：Springer Netherlands
- ISSN：1976-3786
- 卷排序：39
文摘
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.