Punicalagin suppresses osteosarcoma growth and metastasis by regulating NF-κB signaling

J Biol Regul Homeost Agents. 2020 Sep-Oct;34(5):1699-1708. doi: 10.23812/20-23-A.


Osteosarcoma is the most prevailing malignant bone tumor among adolescents. Punicalagin, a polyphenolic compound extracted from pomegranate, possesses many functions such as anti-oxidation, anti-bacterial, anti-virus, and immunosuppression, which can counter the aggressiveness of a variety of cancers such cervical, ovarian and prostate. This study aimed to investigate the inhibitory effect of punicalagin on the proliferation and metastasis of osteosarcoma cells and its potential regulatory mechanisms. Osteosarcoma cell lines (HOS cells, U2OS cells and MG63 cells) were treated with different doses of punicalagin, and the effects on osteosarcoma cell activity were examined in vitro using cell counting kit-8 (CCK-8), colony formation and apoptosis assays. The mobility, migration and invasion abilities of osteosarcoma cells were detected by wound healing and Transwell assays. NF-κB activity was explored by the NF-κB p65 luciferase reporter assay. Western blot was used to investigate the expressions of downstream proteins. We found that punicalagin inhibited the viability of osteosarcoma cells in vitro in dose-dependent and time-dependent manners and promoted apoptosis. In addition, punicalagin could significantly impede the mobility, migration and invasion abilities of osteosarcoma cells. In terms of mechanism, punicalagin down-regulated the expressions of p65, survivin, XIAP, CIAP2 and other proteins, and suppressed the proliferation and metastasis of osteosarcoma cells by repressing NF-κB signaling pathway. In conclusion, it is concluded that punicalagin restrains the growth and metastasis of osteosarcoma by obstructing the NF-κB signal transduction pathway.

Keywords: NF-κB; apoptosis; osteosarcoma; punicalagin.

MeSH terms

  • Apoptosis
  • Bone Neoplasms / drug therapy
  • Bone Neoplasms / pathology*
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Humans
  • Hydrolyzable Tannins / therapeutic use*
  • NF-kappa B / antagonists & inhibitors*
  • NF-kappa B / genetics
  • Osteosarcoma / drug therapy
  • Osteosarcoma / pathology*
  • Signal Transduction / drug effects*


  • Hydrolyzable Tannins
  • NF-kappa B
  • punicalagin