Peimine‐induced apoptosis and inhibition of migration by regulating reactive oxygen species‐mediated MAPK/STAT3/NF‐κB and Wnt/β‐catenin signaling pathways in gastric cancer MKN‐45 cells

Abstract

Peimine (PM), a natural product extracted from Fritillaria, has anti‐inflammatory, drug resistance reversal, and other pharmacological effects. The purpose of this study was to investigate the antitumor effects and the molecular mechanisms of PM using gastric cancer MKN‐45 cells. Cell counting kit‐8 assays were used to evaluate the viability of gastric cancer cells after treatment with PM. The results showed that PM significantly reduced the activity of gastric cancer cells, and the effect was most obvious in MKN‐45 cells. Annexin V‐FITC/propidium iodide staining and flow cytometry were used to assess apoptosis of MKN‐45 cells after PM treatment. Our results showed that PM‐induced apoptosis of MKN‐45 cells. Flow cytometry was also used to determine the mitochondrial membrane potential and reactive oxygen species (ROS) levels, and to assess PM‐induced cell‐cycle arrest. Additionally, Western blot was used to analyze the expression of signaling pathway proteins and the relationship between apoptosis and ROS accumulation. Our findings showed that PM destroyed the mitochondria by diminishing the mitochondrial membrane potential. In addition, PM regulated the mitogen‐activated protein kinase (MAPK), signal transducer and activator of transcription 3, and nuclear factor kappa‐B signaling pathways by promoting the accumulation of ROS in MKN‐45 cells. PM also caused cell‐cycle arrest in the G2/M phase by increasing ROS accumulation. Furthermore, PM inhibited cell migration by regulating the Wnt/β‐catenin pathway. In conclusion, PM plays an anticancer role through endogenous apoptosis pathways and by inhibiting cell migration, and it has the potential to be a useful treatment for gastric cancers.

Crosstalk between CXCL12/CXCR4/ACKR3 and the STAT3 Pathway

“…However, the reciprocal regulatory interactions among STAT3, NFκB, and MAPK induced by CXCL12 are yet to be fully elucidated. Jin et al have documented the regulatory effects of the MAPK/STAT3/NFκB signaling cascade in the treatment of gastric cancer cells [ 141 , 142 ].…”

“…However, the reciprocal regulatory interactions among STAT3, NFκB, and MAPK induced by CXCL12 are yet to be fully elucidated. Jin et al have documented the regulatory effects of the MAPK/STAT3/NFκB signaling cascade in the treatment of gastric cancer cells [141,142]. In a variety of tumor cells, including gastric cancer, glioblastoma, and breast cancer, the activation of the CXCL12/CXCR4 axis has been observed to stimulate the SRC, ERK, and STAT3 pathways.…”

Natural products targeting signaling pathways associated with regulated cell death in gastric cancer: Recent advances and perspectives

“…It was suggested that silymarin facilitated apoptosis in AGS cells by up‐regulating p38 and p‐JNK, as well as decreasing p‐ERK, which indicated that silymarin suppressed GC progression via modulation of the MAPK signaling pathway (Kim et al, 2019). More molecular compounds inducing apoptosis via targeting the MAPK signaling pathway are listed in Table 1 (Fu et al, 2019; Wang, Shen, et al, 2018a, 2019a; Zhang et al, 2021; Zhang, Liu, et al, 2022d). As a result, above results suggests that several natural products promote apoptosis in GC cells by targeting MAPK cascades.…”

Research progress on etiology, pathogenesis and treatment of gastric precancerous lesions

“…Peimine is a pharmaceutical component with anti-inflammatory effects extracted from Zhejiang Fritillary, Zhang T [37] Studies on Fritillin have shown that the substance can regulate apoptosis and inhibit migration induced by reactive oxygen β species in MKN-3 cells of gastric cancer, and have a good effect on gastric cancer treatment. At present, relatively little research has been done on fritine, and its mechanism of action still needs further study.…”