Curcumin inhibits cell proliferation and promotes apoptosis in human osteoclastoma cell through MMP-9, NF-κB and JNK signaling pathways

Int J Clin Exp Pathol. 2015 Jun 1;8(6):6037-45. eCollection 2015.


Curcumin is a polyphenol compound extracted from ginger plant, turmeric, commonly used in a variety of food coloring and flavoring additives. Curcumin has many effects such as anti-inflammatory, anti-tumor, antioxidant and anti-microbial effects. However, the mechanism underlying the anti-cancer effect of curcumin on human osteoclastoma (Giant cell tumor, GCT) cells remains unclear. The objectives of this study were to determine the efficacy of curcumin on proliferation and apoptosis of GCT cells and its related mechanisms. In our study, cell viability, cellular apoptosis and caspase-3 activity of GCT cells were analyzed using 3.3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, flow cytometry (FCM) assay and commercial kits, respectively. Next, MMP-9 gene expression quantity, NF-κB activity and JNK protein expression of GCT cells were tested with real-time polymerase chain reaction (RT-PCR), commercial kits and western blotting assay, respectively. Firstly, MMP-9, NF-κB and JNK inhibitors were added into GCT cells and which was researched the mechanism of curcumin on human GCT cells. In this study, the efficacy of curcumin reduced cell viability, induced cellular apoptosis and increased caspase-3 activity of GCT cells. Furthermore, curcumin inhibited the MMP-9 gene expression quantity and NF-κB activity, and activated JNK protein expression in GCT cells. Meanwhile, down-regulation of MMP-9 gene expression quantity and NF-κB activity could promote the anti-cancer effect of curcumin on cell viability of GCT cells. Interesting, down-regulation of JNK protein expression could also reversed the anti-cancer effect of curcumin on cell viability of GCT cells. Taken together, our results suggest that curcumin inhibits cell proliferation and promotes apoptosis in osteoclastoma cell through suppression of MMP-9 and NF-κB, and activation JNK signaling pathways.

Keywords: Curcumin; JNK; MMP-9; NF-κB; osteoclastoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Apoptosis / drug effects*
  • Bone Neoplasms / drug therapy*
  • Bone Neoplasms / enzymology
  • Bone Neoplasms / genetics
  • Bone Neoplasms / pathology
  • Caspase 3 / metabolism
  • Cell Line, Tumor
  • Cell Proliferation / drug effects*
  • Cell Survival / drug effects
  • Curcumin / pharmacology*
  • Dose-Response Relationship, Drug
  • Giant Cell Tumor of Bone / drug therapy*
  • Giant Cell Tumor of Bone / enzymology
  • Giant Cell Tumor of Bone / genetics
  • Giant Cell Tumor of Bone / pathology
  • Humans
  • JNK Mitogen-Activated Protein Kinases / metabolism*
  • Matrix Metalloproteinase 9 / genetics
  • Matrix Metalloproteinase 9 / metabolism*
  • NF-kappa B / metabolism*
  • Osteoclasts / drug effects*
  • Osteoclasts / enzymology
  • Osteoclasts / pathology
  • Signal Transduction / drug effects
  • Time Factors
  • Tumor Cells, Cultured


  • Antineoplastic Agents, Phytogenic
  • NF-kappa B
  • JNK Mitogen-Activated Protein Kinases
  • CASP3 protein, human
  • Caspase 3
  • MMP9 protein, human
  • Matrix Metalloproteinase 9
  • Curcumin