Proanthocyanidins attenuate breast cancer-induced bone metastasis by inhibiting Irf-3/c-jun activation

Anticancer Drugs. 2019 Nov;30(10):998-1005. doi: 10.1097/CAD.0000000000000852.


We have previously demonstrated the pivotal role of Jnk-mediated Irf-3/c-Jun in regulating nuclear factor kappa-Β ligand (RANKL)-induced osteoclastogenesis. Here, we demonstrated that proanthocyanidins (PACs) target Irf-3 to alleviate breast cancer-induced activation of osteoclasts. We also found that PACs induced apoptosis of osteoclast precursors by upregulating the ratio of bax/bcl-2 and activating caspase-3 activity. Such bone protective effect also could be observed in a bone metastasis model of breast cancer. These findings provided a novel therapeutic intervention targeting abnormal bone metabolism to alleviate bone metastasis of breast cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Bone Neoplasms / drug therapy*
  • Bone Neoplasms / metabolism
  • Bone Neoplasms / secondary*
  • Breast Neoplasms / pathology*
  • Cell Line, Tumor
  • Culture Media, Conditioned / pharmacology
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Interferon Regulatory Factor-3 / genetics
  • Interferon Regulatory Factor-3 / metabolism*
  • Male
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Osteoclasts / drug effects
  • Osteoclasts / metabolism
  • Osteogenesis / drug effects
  • Osteogenesis / physiology
  • Proanthocyanidins / pharmacology*
  • Proto-Oncogene Proteins c-jun / genetics
  • Proto-Oncogene Proteins c-jun / metabolism*


  • Culture Media, Conditioned
  • Interferon Regulatory Factor-3
  • Irf3 protein, mouse
  • Proanthocyanidins
  • Proto-Oncogene Proteins c-jun