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

Abstract

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.

Figure 1

Chemical structure ofcurcumin.

Figure 2

Effect of curcumin on cell viability of GCT cells. **P < 0.01 compared with 0 μM curcumin-treated group.

Figure 3

Effect of curcumin on cellular apoptosis of GCT cells. **P < 0.01 compared with 0 μM curcumin-treated group.

Figure 4

Effect of curcumin on caspase-3 activity of GCT cells. **P < 0.01 compared with 0 μM curcumin-treated group.

Figure 5

Effect of curcumin on MMP-9 of GCT cells. **P < 0.01 compared with 0 μM curcumin-treated group.

Figure 6

MMP-9 inhibitor influences the anti-effect of curcumin on GCT cells. MMP-9 inhibitor influences MMP-9 gene expression quantity (A) and the anti-effect of curcumin on GCT cells (B). **P < 0.01 compared with 0 μM curcumin-treated group, ##P < 0.01 compared with 10 μM curcumin-treated group.

Figure 7

Effect of curcumin on NF-κB activity of GCT cells. **P < 0.01 compared with 0 μM curcumin-treated group.

Figure 8

NF-κB inhibitor influences the anti-effect of curcumin on GCT cells.NF-κB inhibitor influences NF-κB activity (A) and the anti-effect of curcumin on GCT cells (B). **P < 0.01 compared with 0 μM curcumin-treated group, ##P < 0.01 compared with 10 μM curcumin-treated group.

Figure 9

Effect of curcumin on JNK protein expression of GCT cells. **P < 0.01 compared with 0 μM curcumin-treated group.

Figure 10

JNK inhibitor influences the anti-effect of curcumin on GCT cells. JNK inhibitor influences JNK protein expression by western blotting assays (A), statistical analysis of JNK protein expression (B) and the anti-effect of curcumin on GCT cells (C). **P < 0.01 compared with 0 μM curcumin-treated group, ##P < 0.01 compared with 10 μM curcumin-treated group.