Schisandrin B exerts anticancer effects on human gastric cancer cells through ROS-mediated MAPK, STAT3, and NF-κB pathways

Abstract

Schisandrin B (Sch B) is a monomer with anti-cancer and anti-inflammatory effects, which are isolated from the plant Schisandra chinensis (Turcz) Baillon. We investigated the anti-gastric cancer (GC) effects of Sch B and its underlying molecular mechanisms. The Cell Counting Kit-8 assay was used to determine the effects of Sch B on the viability of GC and normal cell lines. Hoechst/propidium iodide staining and flow cytometry were used to assess the apoptosis induction of Sch B. Western blotting was used to evaluate the effects of Sch B on downstream apoptotic proteins. The DCFH-DA fluorescent probe was used to assess the regulatory effects of Sch B on reactive oxygen species (ROS) levels and related signaling pathways in GC cells. The results showed that Sch B could regulate the phosphorylation level of mitogen-activated protein kinase (MAPK) by upregulating ROS accumulation in gastric cancer cells, and then reduce the expression of nuclear factor kappa B (NF-κB) and phosphorylated transcription 3 (p-STAT3). In addition, Sch B downregulated the cell cycle proteins cyclin-dependent kinase 2/4/6 and cyclin D1/E, and arrested cells in the G0/G1 phase. Moreover, it also inhibited cell migration, which was reversed with Nacetylcysteine pretreatment. In summary, Sch B has killing effects on GC cells by upregulating the production of intracellular ROS and regulating the MAPK/STAT3/NF-κB signaling pathway, leading to the migration arrest and apoptosis of GC cells.