Korean Red Ginseng inhibits apoptosis in neuroblastoma cells via estrogen receptor β-mediated phosphatidylinositol-3 kinase/Akt signaling

Abstract

BackgroundGinseng 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.MethodsHuman 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.ResultsPretreating 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.ConclusionCollectively, the data indicate that KRG represses oxidative stress-induced apoptosis by enhancing PI3K/Akt signaling via upregulation of ER-β expression.

Different anticancer effects of Saxifragifolin A on estrogen receptor-positive and estrogen receptor-negative breast cancer cells

“…Cell cytotoxicity was measured by quantitative colorimetric assay with a 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenylterazolium bromide (MTT) assay as described elsewhere (Nguyen et al, 2015). Breast cancer cells were seeded at a concentration of 1 × 10 5 cells/well in 96-well plates and treated with Saxi A for 24 h. The cells were washed once with D-PBS and incubated with 25 mg/ml of MTT (Sigma, St. Louis, MO) for 4 h at 37°C and 5% CO 2 .…”

Neuroprotective effect of Korea Red Ginseng extract on 1-methyl-4-phenylpyridinium-induced apoptosis in PC12 Cells

“…Ginsenoside Rg2 reduced glutamate-induced cell death significantly through mechanisms related to anti-apoptosis and anti-oxidation in PC12 cells (Li et al 2007). A few studies also reported that the water extract of KRG protected cultured cortical cells from amyloid-β-induced apoptosis (Kim et al 2014) and repressed apoptosis in SK-N-SH cells by suppressing oxidative stress (Nguyen et al 2015). Therefore, the ginsenosides may play an important role in the observed prevention of apoptotic cell death in response to the KRG extract, but the possibility that other substances are involved in the anti-apoptotic effect still remains.…”

Protective Effect of Korean Red Ginseng on Cisplatin Ototoxicity: Is It Effective Enough?

“…While the intrinsic pathway activates with the release of cytochrome-c from the mitochondria, the extrinsic pathway activates by ligand binding to death receptors such as Fas and tumor necrosis factor receptor-1 (TNFR1) [3-7, 9, 10] . Some candidate agents such as sodium thiosulfate, D-or L-methionine, lipoic acid, N-acetyl cysteine, acetyl L-carnitine, alpha tocopherol, and resveratrol were studied both in vitro and in vivo to analyze their protective effects against CDDP-induced ototoxicity [7,16,[18][19][20][21] . However, none of them are currently approved for usage against CDDP-induced ototoxicity.…”

“…These studies revealed that KRG mainly works by inhibition of some proapoptotic genes such as caspase-1, caspase-3, and the TNF family of genes and by enhancement of antiapoptotic gene expression such as bcl-2 [8][9][10][11][12][13] . On the other hand, KRG has antiapoptotic effects on neuronal tissues [18] . It was shown that this effect mainly works by up regulation of the p13K/Akt signaling pathway, which is a cell survival pathway.…”

“…It was shown that this effect mainly works by up regulation of the p13K/Akt signaling pathway, which is a cell survival pathway. Activation of this pathway inhibits apoptosis by decreasing p53 and caspase-3 expression while also increasing expression of genes in the bcl2 family [8,11,18] . KRG has also been shown to be an otoprotective agent following cochlear injury associated with noise-induced hearing loss [25] .…”