Schizandrin A induces the apoptosis and suppresses the proliferation, invasion and migration of gastric cancer cells by activating endoplasmic reticulum stress

Abstract

Apart from its basic antioxidant and anti-inflammatory properties, schizandrin A (SchA), which is isolated from Fructus schisandra, can exert anticancer effects on multiple cancer types. However, to the best of our knowledge, there has been no study identifying the impacts of SchA on gastric cancer (GC). Therefore, the aim of the present study was to identify how SchA functioned to affect the progression of GC. To investigate the role of SchA in GC development, Cell Counting Kit-8, colony formation, wound healing and Transwell assays were conducted to assess the viability, proliferation, migration and invasion of AGS cells, respectively. Then, the apoptosis rate and apoptosis-and endoplasmic reticulum (ER) stress-related protein expression levels in AGS cells exposed to SchA were detected via TUNEL assays and western blotting, respectively. Subsequently, the aforementioned functional assays were performed again in AGS cells exposed to both SchA and the ER stress inhibitor 4-phenylbutyric acid (4-PBA) for the confirmation of the effect of SchA on ER stress in GC. It was found that SchA markedly decreased the viability, proliferation, migration and invasion, while it induced the apoptosis of AGS cells. Moreover, the markers of ER stress were elevated by SchA treatment in AGS cells. Nevertheless, 4-PBA reversed the effects of SchA on the viability, proliferation, migration, invasion and apoptosis of AGS cells, accompanied by decreased expression of ER stress markers. In conclusion, the present study demonstrated that SchA induced the apoptosis and suppressed the proliferation, invasion and migration of GC cells by activating ER stress, which provides a theoretical basis for the use of SchA in the treatment of GC.

Baicalein facilitates gastric cancer cell apoptosis by triggering endoplasmic reticulum stress via repression of the PI3K/AKT pathway

“…Excessive ERS contributes to apoptosis and blockage of ERS attenuated scoulerine-induced apoptosis in colorectal cancer cells [ 43 ]. Consistently, schizandrin A stimulates apoptosis and impedes GC cell growth by activating ERS [ 44 ]. Baicalein induces hepatocellular carcinoma apoptosis by triggering ERS, presumably by lowering the anti-apoptotic regulators and elevating intracellular Ca 2+ [ 45 ].…”

The dual effect of endoplasmic reticulum stress in digestive system tumors and intervention of Chinese botanical drug extracts: a review

“…Baill with antioxidant and antitumor effects (Xiang LB et al, 2023;Zeng J et al, 2023). Pu H et al (2021) found that schizandrin A (10, 20, 30, 40, 50 μg/mL for 24, 48, 72 h) was able to upregulate the expression of p-PERK, p-eIF2α, and CHOP in GES-1 and AGS cells, inhibiting GC cells' viability and inducing apoptosis, which could be reversed by the ERS inhibitor 4-PBA. Another study demonstrated that schizandrin B (12.5, 25, 50, 100, 150, 200 μmol/L for 24 h) inhibited tumor cell viability and induced apoptosis through the upregulation of Bax, Caspase-3, Frontiers in Pharmacology frontiersin.org CHOP, p-PERK, p-eIF2α, and ATF4 expression, and downregulation of p-PI3K and p-Akt expression to regulate ERS and promote apoptosis in GC cells BGC-823 (Ge YN et al, 2022).…”

Traditional Chinese medicine suppressed cancer progression by targeting endoplasmic reticulum stress responses: A review

“…Head and neck cancer 29 Sinomenine hydrochloride Reverse EMT through autophagy via ERS [45] Digestive tract tumor 30 Corilagin GRP78-caspase-7 and caspase-12 [46] 31 Schizandrin A PERK/eIF2α/CHOP pathways [47] Gynecologic urogenital tumors 32 Betulinic acid GRP78-PERK-p-eIF2α-β-catenin and c-Myc [48] 33 Sini San GRP78-chronic psychological stress-Wnt/βcatenin [49] 34 Matrine PERK-p-eIF2α-ATF4-CHOP pathways-E-cadherin [50] 35…”

“…[ 46 ] Schisandra chinensis A inhibits the proliferation, invasion, and metastasis of GES-1 human gastric epithelial cells and AGS gastric cancer cells partly through the PERK/eIF2α/CHOP signaling pathway. [ 47 ]…”