Schizandra chinensisextracts induce apoptosis in human gastric cancer cells via JNK/p38 MAPK activation and the ROS-mediated/mitochondria-dependent pathway

Abstract

Objectives: This study investigates the mechanism of SCE-induced apoptosis in AGS human gastric cancer cells. Materials and methods: SCE concentrations from 100 to 400 mg/ml were used. Cell viabilities were determined using MTT assay. Members of the Bcl-2 family and Bax were detected by Western blotting. RT-PCR was performed to measure the expression level of the Fas/FasL pro-apoptotic genes.Results: SCE inhibited the proliferation AGS cells for 24 or 72 h (inhibition by 3.1% ± 5.2% at 100 mg/ml and 87.3% ± 7.6% at 400 mg/ml at 24 h and by 40.2% ± 5.3% 100 mg/ml and 95.3% ± 1.3% 400 mg/ml at 72 h) and increased the sub-G1 phase (25.3% ± 5.2% at 100 mg/ml and 370.2% ± 7.2% at 400 mg/ml) and the mitochondrial membrane depolarization (11.2% ± 2.1% at 100 mg/ml and 311.5% ± 6.1% at 400 mg/ml). The SCE-induced apoptotic cell death showed the down-regulation of Bcl-2, but up-regulation of Bax. Subsequently, SCE increased the expression level of Fas/FasL, activated caspase-9 and -3, and increased reactive oxygen species generation. Also, JNK II inhibitor or a p38 MAPK inhibitor inhibited SCE-induced cell death. Discussion and conclusion: These results indicate that SCE might be an effective chemotherapeutic for the treatment of human gastric cancer.

Reactive oxygen species‐mediated phosphorylation of p38 signaling is critically involved in apoptotic effect of Tanshinone I in colon cancer cells

“…There are accumulating evidences that MAPK pathways including JNK, p38, and ERK are involved in cell survival and apoptosis in several cancer cells following exposure to various stimuli (Milone et al, ). Additionally, it was reported that ROS affects MAPK signaling (Kim et al, ; Weh, Aiyer, Howell, & Kresty, ), and also, intercellular ROS production induces MAPK activation during apoptosis (Hua et al, ; Y. Zhu et al, ). In this study, Tan I increased phosphorylation of p38 and JNK but not ERK in HCT116 and HT29 cells.…”

Dihydrotanshinone induces apoptosis of SGC7901 and MGC803 cells via activation of JNK and p38 signalling pathways

“…Accumulating evidence indicates that activation of MAPK, especially the JNK/p38-MAPK is associated with gastric cell apoptosis induction and considered as a promising therapeutic target (Chun et al 2013;Kim et al 2015). The JNK/p38-MAPK activation leads to permeabilization of outer mitochondrial membrane resulting in mitochondrial cytochrome c release into the cytosol during cell apoptosis progresses .…”

Di(2-ethylhexyl) phthalate induces apoptosis through mitochondrial pathway in GC-2spd cells

“…Thus, Bcl‐2/Bax ratio is very important in apoptosis regulation. The down‐regulation of Bcl‐2 protein and the up‐regulation of Bax protein can cause MOMP and induce cell apoptosis eventually (Kim et al, ). The present study showed an increasing expression of Bax at both mRNA and protein levels in GC‐2spd cells after exposure to DEHP, accompanying with the decreasing expression of Bcl‐2.…”