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

Abstract

BackgroundCelastrol, 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.MethodsWe 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.ResultsCelastrol 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.ConclusionsIn this study, we demonstrated that the effect of celastrol on apoptosis is due to miR-146a inhibition of NF-κB activity.

Celastrol Induces Apoptosis of Gastric Cancer Cells by miR-21 Inhibiting PI3K/Akt-NF-κB Signaling Pathway

“…Our previous study showed that celastrol could induce apoptosis of gastric cancer cells [14]. To further explore the molecular mechanism underlying celastrol-induced apoptosis, we examined the effect of celastrol on the PI3K/Akt pathway by measuring levels of phospho-Akt and total Akt.…”

“…It has been reported that celastrol plays an important role in inhibiting proliferation and inducing apoptosis of a wide variety of human tumor cell types including gastric cancer [14,17,18,19,20]. A number of studies have suggested that miR-21 activation plays a pivotal role in gastric cancer cell survival [21].…”

“…The transcription factor NF-κB is also activated in tumorigenic processes including gastric cancer and there are numerous indications of interaction between the Akt and NF-κB pathways [11,12,13]. In our previous studies, it has been shown that celastrol elicits an antitumor effect against gastric cancer by inhibition of NF-kB activation [14]. Therefore, the aim of this study was to evaluate whether the miR-21-regulated PI3K/Akt-NF-κB signaling pathway was involved in the antitumor effect of celastrol in human gastric cancer.…”

Quercetin inhibits proliferation and invasion acts by up-regulating miR-146a in human breast cancer cells

“…Decrease of miR-146a expression has been reported in multiple human cancer types, involving prostate [23], lung [20,29], gastric [30], and breast [31] cancers. As a result, we evaluated the up-regulation effect of quercetin on miR146a expression in MCF-7 and MDA-MB-231 human breast cancer calls and human breast cancer xenograft model.…”

Apolipoprotein E Epsilon 4 Enhances the Association between the rs2910164 Polymorphism of miR-146a and Risk of Atherosclerotic Cerebral Infarction

“…As shown in our results, the reduction of miR-146a expression increased IRAK1 levels significantly in CC genotypes in ApoE 4( ) carries. Reduction of miR-146a expression can reverse the effect of NF-B activity inhibition 49) . ApoE controls inflammation by suppressing inflammatory NF-B signaling 24) .…”