Morin inhibits osteosarcoma migration and invasion by suppressing urokinase plasminogen activator through a signal transducer and an activator of transcription 3

Environ Toxicol. 2024 Apr;39(4):2024-2031. doi: 10.1002/tox.24100. Epub 2023 Dec 13.

Abstract

Osteosarcoma, the most common primary bone cancer that affects adolescents worldwide, has the early metastatic potential to be responsible for high mortality rates. Morin has a multipurpose role in numerous cancers, whereas little is known about its role in osteosarcoma migration and invasion. Therefore, we hypothesized that morin suppresses the invasive activities and the migratory potential of human osteosarcoma cells. Our results showed that morin reduced migration and invasion capabilities in human osteosarcoma U2OS and HOS cells. Moreover, morin inhibited the urokinase plasminogen activator (uPA) expression through a signal transducer and an activator of transcription-3 (STAT3) phosphorylation. After STAT3 overexpression, the decrease of the migratory potential and uPA expression caused by 100 μM of morin in U2OS cells was countered, indicating that STAT3 contributes to the antimetastatic property of morin in human osteosarcoma cells by reducing uPA. In conclusion, morin may be a potential candidate for the antimetastatic treatment of human osteosarcoma.

Keywords: STAT3; migration; morin; osteosarcoma; uPA.

MeSH terms

  • Adolescent
  • Bone Neoplasms* / drug therapy
  • Cell Line, Tumor
  • Cell Movement
  • Flavones*
  • Flavonoids / pharmacology
  • Humans
  • Neoplasm Invasiveness / pathology
  • Osteosarcoma* / drug therapy
  • Osteosarcoma* / pathology
  • Urokinase-Type Plasminogen Activator / metabolism

Substances

  • Urokinase-Type Plasminogen Activator
  • morin
  • Flavonoids
  • Flavones