Limits...
Celastrol induces apoptosis of gastric cancer cells by miR-146a inhibition of NF-κB activity.

Sha M, Ye J, Zhang LX, Luan ZY, Chen YB - Cancer Cell Int. (2013)

Bottom Line: Finally, the effect of miR-146a on celastrol-induced anti-tumor activity was assessed using miR-146a inhibitor.Celastrol also reduced IκB phosphorylation, nuclear P65 protein levels and NF-κB activity.In this study, we demonstrated that the effect of celastrol on apoptosis is due to miR-146a inhibition of NF-κB activity.

View Article: PubMed Central - HTML - PubMed

Affiliation: Institute of Clinical medicine, Taizhou people's Hospital affiliated of Nantong University of medicine, 210 Yingchun, Taizhou, Jiangsu Province, 225300, China. tzrmyy5211@163.com.

ABSTRACT

Background: Celastrol, a plant triterpene, is known to play important role in inhibiting proliferation and inducing apoptosis of gastric cancer cells. In the present study, the mechanism of celastrol on gastric cancer cells apoptosis was examined.

Methods: We assessed effect of celastrol on NF-κB signaling pathway in gastric cancer cells using western blot and luciferase reporter assay. The real-time PCR was used to evaluate the effect of celastrol on miR-146a expression, and miR-146a mimic to evaluate whether over-expression of miR-146a can affect NF-κB activity. Finally, the effect of miR-146a on celastrol-induced anti-tumor activity was assessed using miR-146a inhibitor.

Results: Celastrol decreased gastric cancer cells viability in a dose-dependent. Celastrol also reduced IκB phosphorylation, nuclear P65 protein levels and NF-κB activity. Furthermore, Celastrol could increase miR-146a expression and up-regulation of miR-146a expression could suppress NF-κB activity. More important, down-regulation of miR-146a expression can reverse the effect of celastrol on NF-κB activity and apoptosis in gastric cancer cells.

Conclusions: In this study, we demonstrated that the effect of celastrol on apoptosis is due to miR-146a inhibition of NF-κB activity.

No MeSH data available.


Related in: MedlinePlus

Celastrol repressed viability of gastric cancer cells and NF-κB signaling pathway. Exposure to various concentrations of celastrol resulted in dose- and time-dependent growth inhibition of BGC-823 cells (A), SGC-7901 cells (B), MGC-803 cells (C) and GES-1 cells (D). Celastrol inhibited phosphorylation of IκB and nuclear p65 content in dose-dependent manner (E). Celastrol decreased NF-κB transcriptional activity in BGC-823 cells, SGC-7901 cells and MGC-803 cells in a dose-dependent manner (F). *P < 0.05, indicate significant differences from the respective control groups.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC3672015&req=5

Figure 1: Celastrol repressed viability of gastric cancer cells and NF-κB signaling pathway. Exposure to various concentrations of celastrol resulted in dose- and time-dependent growth inhibition of BGC-823 cells (A), SGC-7901 cells (B), MGC-803 cells (C) and GES-1 cells (D). Celastrol inhibited phosphorylation of IκB and nuclear p65 content in dose-dependent manner (E). Celastrol decreased NF-κB transcriptional activity in BGC-823 cells, SGC-7901 cells and MGC-803 cells in a dose-dependent manner (F). *P < 0.05, indicate significant differences from the respective control groups.

Mentions: The inhibitory effects of celastrol on the growth of gastric cancer cells and normal gastric epithelial cells were evaluated using MTT assays. Celastrol treatment inhibited the growth of BGC-823, SGC-7901 and MGC-803 cells in a dose- and time-dependent manner (Figure 1A, 1B and 1C). And the IC 50 value at 72 h after treatment was 0.989 μM (BGC-823 cells), 0.798 μM (SGC-7901 cells) and 1.98 μM (MGC-803 cells). Normal gastric epithelial cells showed more resistance to the cytotoxicity effect of celastrol. And the IC 50 value at 72 h was 8.16 μM for GES-1 cells (Figure 1D).


Celastrol induces apoptosis of gastric cancer cells by miR-146a inhibition of NF-κB activity.

Sha M, Ye J, Zhang LX, Luan ZY, Chen YB - Cancer Cell Int. (2013)

Celastrol repressed viability of gastric cancer cells and NF-κB signaling pathway. Exposure to various concentrations of celastrol resulted in dose- and time-dependent growth inhibition of BGC-823 cells (A), SGC-7901 cells (B), MGC-803 cells (C) and GES-1 cells (D). Celastrol inhibited phosphorylation of IκB and nuclear p65 content in dose-dependent manner (E). Celastrol decreased NF-κB transcriptional activity in BGC-823 cells, SGC-7901 cells and MGC-803 cells in a dose-dependent manner (F). *P < 0.05, indicate significant differences from the respective control groups.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3672015&req=5

Figure 1: Celastrol repressed viability of gastric cancer cells and NF-κB signaling pathway. Exposure to various concentrations of celastrol resulted in dose- and time-dependent growth inhibition of BGC-823 cells (A), SGC-7901 cells (B), MGC-803 cells (C) and GES-1 cells (D). Celastrol inhibited phosphorylation of IκB and nuclear p65 content in dose-dependent manner (E). Celastrol decreased NF-κB transcriptional activity in BGC-823 cells, SGC-7901 cells and MGC-803 cells in a dose-dependent manner (F). *P < 0.05, indicate significant differences from the respective control groups.
Mentions: The inhibitory effects of celastrol on the growth of gastric cancer cells and normal gastric epithelial cells were evaluated using MTT assays. Celastrol treatment inhibited the growth of BGC-823, SGC-7901 and MGC-803 cells in a dose- and time-dependent manner (Figure 1A, 1B and 1C). And the IC 50 value at 72 h after treatment was 0.989 μM (BGC-823 cells), 0.798 μM (SGC-7901 cells) and 1.98 μM (MGC-803 cells). Normal gastric epithelial cells showed more resistance to the cytotoxicity effect of celastrol. And the IC 50 value at 72 h was 8.16 μM for GES-1 cells (Figure 1D).

Bottom Line: Finally, the effect of miR-146a on celastrol-induced anti-tumor activity was assessed using miR-146a inhibitor.Celastrol also reduced IκB phosphorylation, nuclear P65 protein levels and NF-κB activity.In this study, we demonstrated that the effect of celastrol on apoptosis is due to miR-146a inhibition of NF-κB activity.

View Article: PubMed Central - HTML - PubMed

Affiliation: Institute of Clinical medicine, Taizhou people's Hospital affiliated of Nantong University of medicine, 210 Yingchun, Taizhou, Jiangsu Province, 225300, China. tzrmyy5211@163.com.

ABSTRACT

Background: Celastrol, a plant triterpene, is known to play important role in inhibiting proliferation and inducing apoptosis of gastric cancer cells. In the present study, the mechanism of celastrol on gastric cancer cells apoptosis was examined.

Methods: We assessed effect of celastrol on NF-κB signaling pathway in gastric cancer cells using western blot and luciferase reporter assay. The real-time PCR was used to evaluate the effect of celastrol on miR-146a expression, and miR-146a mimic to evaluate whether over-expression of miR-146a can affect NF-κB activity. Finally, the effect of miR-146a on celastrol-induced anti-tumor activity was assessed using miR-146a inhibitor.

Results: Celastrol decreased gastric cancer cells viability in a dose-dependent. Celastrol also reduced IκB phosphorylation, nuclear P65 protein levels and NF-κB activity. Furthermore, Celastrol could increase miR-146a expression and up-regulation of miR-146a expression could suppress NF-κB activity. More important, down-regulation of miR-146a expression can reverse the effect of celastrol on NF-κB activity and apoptosis in gastric cancer cells.

Conclusions: In this study, we demonstrated that the effect of celastrol on apoptosis is due to miR-146a inhibition of NF-κB activity.

No MeSH data available.


Related in: MedlinePlus