Allyl isothiocyanate inhibits cell migration and invasion in human gastric cancer AGS cells via affecting PI3K/AKT and MAPK signaling pathway in vitro

Environ Toxicol. 2023 Oct;38(10):2287-2297. doi: 10.1002/tox.23864. Epub 2023 Jun 15.

Abstract

Metastasis is commonly occurred in gastric cancer, and it is caused and responsible for one of the major cancer-related mortality in gastric cancer patients. Allyl isothiocyanate (AITC), a natural product, exhibits anticancer activities in human many cancer cells, including gastric cancer. However, no available report shows AITC inhibits gastric cancer cell metastasis. Herein, we evaluated the impact of AITC on cell migration and invasion of human gastric cancer AGS cells in vitro. AITC at 5-20 μM did not induce significant cell morphological damages observed by contrast-phase microscopy but decreased cell viability assayed by flow cytometry. After AGS cells were further examined by atomic force microscopy (AFM), which indicated AITC affected cell membrane and morphology in AGS cells. AITC significantly suppressed cell motility examined by scratch wound healing assay. The results of the gelatin zymography assay revealed that AITC significantly suppressed the MMP-2 and MMP-9 activities. In addition, AITC suppressed cell migration and invasion were performed by transwell chamber assays at 24 h in AGS cells. Furthermore, AITC inhibited cell migration and invasion by affecting PI3K/AKT and MAPK signaling pathways in AGS cells. The decreased expressions of p-AKTThr308 , GRB2, and Vimentin in AGS cells also were confirmed by confocal laser microscopy. Our findings suggest that AITC may be an anti-metastasis candidate for human gastric cancer treatment.

Keywords: MAPK signaling pathway; MMP-2 and MMP-9; PI3K/AKT signaling pathway; allyl isothiocyanate (AITC); human gastric cancer AGS cells; uPA.

MeSH terms

  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Humans
  • Neoplasm Invasiveness
  • Phosphatidylinositol 3-Kinases / metabolism
  • Proto-Oncogene Proteins c-akt* / metabolism
  • Signal Transduction
  • Stomach Neoplasms* / metabolism

Substances

  • 2,3,4-tri-O-acetylarabinopyranosyl isothiocyanate
  • Proto-Oncogene Proteins c-akt
  • allyl isothiocyanate
  • Phosphatidylinositol 3-Kinases