title: Korean Red Ginseng inhibits apoptosis in neuroblastoma cells via estrogen receptor β-mediated phosphatidylinositol-3 kinase/Akt signaling.
abstract: BACKGROUND
  Ginseng has been shown to exert antistress effects both in vitro and in vivo. However, the effects of ginseng on stress in brain cells are not well understood. This study investigated how Korean Red Ginseng (KRG) controls hydrogen peroxide-induced apoptosis via regulation of phosphatidylinositol-3 kinase (PI3K)/Akt and estrogen receptor (ER)-β signaling.
  
  
  METHODS
  Human neuroblastoma SK-N-SH cells were pretreated with KRG and subsequently exposed to H2O2. The ability of KRG to inhibit oxidative stress-induced apoptosis was assessed in MTT cytotoxicity assays. Apoptotic protein expression was examined by Western blot analysis. The roles of ER-β, PI3K, and p-Akt signaling in KRG regulation of apoptosis were studied using small interfering RNAs and/or target antagonists.
  
  
  RESULTS
  Pretreating SK-N-SH cells with KRG decreased expression of the proapoptotic proteins p-p53 and caspase-3, but increased expression of the antiapoptotic protein BCL2. KRG pretreatment was also associated with increased ER-β, PI3K, and p-Akt expression. Conversely, ER-β inhibition with small interfering RNA or inhibitor treatment increased p-p53 and caspase-3 levels, but decreased BCL2, PI3K, and p-Akt expression. Moreover, inhibition of PI3K/Akt signaling diminished p-p53 and caspase-3 levels, but increased BCL2 expression.
  
  
  CONCLUSIONS
  Collectively, the data indicate that KRG represses oxidative stress-induced apoptosis by enhancing PI3K/Akt signaling via upregulation of ER-β expression.
authors.affiliation: School of Pharmacy, Sungkyunkwan University, Su-Won, Korea.
authors.forename: Cuong Thach
authors.initials: CT
authors.lastname: Nguyen
authors.affiliation: School of Pharmacy, Sungkyunkwan University, Su-Won, Korea.
authors.forename: Truc Thanh
authors.initials: TT
authors.lastname: Luong
authors.affiliation: School of Pharmacy, Sungkyunkwan University, Su-Won, Korea.
authors.forename: Gyu-Lee
authors.initials: GL
authors.lastname: Kim
authors.affiliation: School of Pharmacy, Sungkyunkwan University, Su-Won, Korea.
authors.forename: Suhkneung
authors.initials: S
authors.lastname: Pyo
authors.affiliation: School of Pharmacy, Sungkyunkwan University, Su-Won, Korea.
authors.forename: Dong-Kwon
authors.initials: DK
authors.lastname: Rhee
keywords: Panax ginseng; apoptosis; estrogen receptor-β; oxidative stress; phosphatidylinositol-3 kinase/Akt signaling