Gö6983 attenuates breast cancer-induced osteolysis by the apoptotic pathway

Cell Biol Int. 2020 Mar;44(3):838-847. doi: 10.1002/cbin.11281. Epub 2019 Dec 26.

Abstract

Bone metastasis caused by breast cancer leads to significant complications in treatment, and the resulting osteolysis considerably affects patients' overall survival and quality of life. Gö6983 is a broad spectrum protein kinase C inhibitor. In this study, based on our finding that the Gö6983 inhibits osteolysis, we applied Gö6983 to the MDA-MB-231 breast cancer-induced mouse bone metastasis model. And we found that Gö6983 has a strong inhibitory effect on the tumorigenic model of breast cancer by promoting the mitochondrial apoptosis pathway. Our study, therefore, demonstrates that Gö6983 has a potential inhibitory effect on breast cancer-induced osteoclast activation and provides mechanistic insight that may prove useful for designing future treatments.

Keywords: Gö6983; RANKL; osteoclast; protein kinase C.

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Bone Neoplasms* / drug therapy
  • Bone Neoplasms* / secondary
  • Breast Neoplasms* / complications
  • Breast Neoplasms* / pathology
  • Cell Differentiation / drug effects
  • Cell Line, Tumor
  • Indoles* / pharmacology
  • Indoles* / therapeutic use
  • Macrophages
  • Maleimides* / pharmacology
  • Maleimides* / therapeutic use
  • Mice
  • Mice, Inbred C57BL
  • Mice, Nude
  • Mitochondria / drug effects
  • Osteoclasts / drug effects*
  • Osteoclasts / pathology
  • Osteolysis* / drug therapy
  • Osteolysis* / etiology
  • Protein Kinase Inhibitors* / pharmacology
  • Protein Kinase Inhibitors* / therapeutic use

Substances

  • 2-(1-(3-dimethylaminopropyl)-5-methoxyindol-3-yl)-3-(1H-indol-3-yl)maleimide
  • Indoles
  • Maleimides
  • Protein Kinase Inhibitors