Apigenin-induced Apoptosis is Reduced via Endoplasmic Reticulum Stress and ATF6/PERK Signaling in Human Gastric Cancer Cells

Abstract

Background Apigenin effectively inhibits the growth of human gastric carcinoma SGC-7901 cells and induces apoptosis as well. This study investigated the effects of ATF6 and PERK signaling pathways in unfolded protein response (UPR) and endoplasmic reticulum stress (ERS) on the apoptosis induced by apigenin in human gastric carcinoma SGC-7901 cells. Materials and Methods SGC-7901 cells were cultured with apigenin and tunicamycin for 48 h or with apigenin for 12–48 h. CCK-8 was used to determine cell viability. The mRNA expression level was detected by RT-qPCR. The expression of related proteins was explored by Western blot. The apoptosis rate of cells and cell-cycle arrest were evaluated by flow cytometer. Results The results of CCK-8 confirmed that apigenin could induce apoptosis of SGC-7901 cells. In the apigenin-treated cells group, the protein and mRNA levels of GRP78 and GRP94 dose- and time-dependently increased. Additionally, apigenin-activated UPR components PERK and ATF6. However, apigenin exerted no influence on CHOP expression or JNK activation. Pretreatment with 4-PBA significantly increased the apigenin-triggered apoptosis in SCG-7901 cells ( p < 0.05). Conclusion The results revealed the protective effect of UPR performance on apigenin-triggered apoptosis in SGC-7901 cells.