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Pharmacology. 2014;93(1-2):39-46. doi: 10.1159/000357683. Epub 2014 Jan 15.

Celastrol induces apoptosis of gastric cancer cells by miR-21 inhibiting PI3K/Akt-NF-κB signaling pathway.

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  • 1Institute of Clinical Medicine, Taizhou People's Hospital, Nantong University of Medicine, Taizhou, China.

Abstract

OBJECTIVE:

Celastrol, a plant triterpene, has anticancer effects by increase of apoptosis. In the present study, the mechanism of celastrol on gastric cancer cell apoptosis was examined.

METHODS:

The effect of celastrol on PI3K/Akt and the NF-κB signaling pathway was evaluated with Western blot and luciferase reporter assay. miR-21 expression was determined using real-time PCR. miR-21 inhibitor and miR-21 mimic were used to downregulate and upregulate miR-21 expression, respectively.

RESULTS:

It was identified that celastrol was capable of inducing apoptosis of gastric cancer cells, which was mediated via inhibiting the activation of PI3K/Akt and NF-κB. A strong activator of Akt, IGF-1 restored NF-κB activity in cells treated with celastrol. Celastrol could also significantly suppress miR-21 expression. Furthermore, miR-21 inhibitor could decrease phospho-Akt expression and NF-κB activity. Notably, upregulation of miR-21 expression can increase PI3K/Akt and NF-κB activity and decrease apoptosis of gastric cancer cells treated with celastrol, which could be reversed by PI3K inhibitor.

CONCLUSIONS:

Our data revealed that the effect of celastrol on apoptosis was due to miR-21 inhibiting the PI3K/Akt-dependent NF-κB pathway.

PMID:
24434352
DOI:
10.1159/000357683
[PubMed - indexed for MEDLINE]
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