Dihydromyricetin inhibits cancer cell migration and matrix metalloproteinases-2 expression in human nasopharyngeal carcinoma through extracellular signal-regulated kinase signaling pathway

Environ Toxicol. 2022 May;37(5):1244-1253. doi: 10.1002/tox.23480. Epub 2022 Feb 3.

Abstract

Nasopharyngeal carcinoma (NPC) is endemic in Southeast Asia and the main cause of treatment failure is metastasis. A lot of biological and pharmacological actions of dihydromyricetin (DHM) have been reported such as regulating glucose and anti-cancer effects. The effects of DHM on the cancer invasion and migration of NPC, however, are still unclear. We therefore investigated the in vitro anti-metastatic properties of DHM on three human NPC cell lines (HONE-1, NPC-39, and NPC-BM), as well as the underlying signaling pathways. Our study revealed that DHM could suppress the migration and invasion in NPC cells. Gelatin zymography assay and western blotting assays demonstrated that DHM suppressed the enzyme activity and protein expression of matrix metalloproteinases-2 (MMP-2). Mitogen-activated protein kinases were also investigated to elucidate the signaling pathway, which showed that phosphorylation of extracellular signal-regulated kinase 1 and 2 (ERK1/2) was inhibited after the treatment of DHM. In conclusion, our data revealed that DHM inhibited the migration and invasion of NPC cells by suppressing the expression of MMP-2 via down regulating the ERK1/2 signaling pathway.

Keywords: MMP-2; dihydromyricetin; migration; nasopharyngeal carcinoma.

MeSH terms

  • Cell Line, Tumor
  • Cell Movement
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Flavonols
  • Humans
  • MAP Kinase Signaling System
  • Matrix Metalloproteinase 2* / metabolism
  • Nasopharyngeal Carcinoma / pathology
  • Nasopharyngeal Neoplasms* / pathology
  • Neoplasm Invasiveness
  • Signal Transduction

Substances

  • Flavonols
  • Extracellular Signal-Regulated MAP Kinases
  • Matrix Metalloproteinase 2
  • dihydromyricetin