Dehydrocostus lactone, a natural sesquiterpene lactone, suppresses the biological characteristics of glioma, through inhibition of the NF-κB/COX-2 signaling pathway by targeting IKKβ.

Dehydrocostus lactone (DHE), a natural sesquiterpene lactone, has been used for treatment of various diseases with its anti-inflammatory activity. Recently, it has caused extensive interest in researchers due to it has anti-cancer abilities in some types of carcinomas. However, the anti-cancer effect and mechanism of DHE in glioma remains unclear. The present study conducted to determine the biological effects of DHE on the glioblastoma cells, as well as the mechanisms underlying these effects. After treatment with DHE, the glioblastoma (U118, U251 or U87) cells were significantly inhibited in their viability, proliferation and migration. At the meantime, DHE also induced mitochondria-mediated apoptosis by promoting the release of cytochrome c into cytosol, which activating caspase signaling pathway. Furthermore, our results fully demonstrate that DHE significantly suppressed COX-2 expression by inhibiting the phosphorylation of IKKβ via targeting the ATP-binding site, thereby abrogating NF-κB binding and p300 recruitment to COX-2 promoter. Moreover, the current study firstly demonstrated that DHE can cross blood-brain barrier (BBB). In addition, treatment with DHE markedly inhibited neoplastic weight and volume without the notable adverse effects in the xenograft nude mice model, and these effects may be mediated through inhibition of the IKKβ/NF-κB/COX-2 signaling pathway. These findings provide the pharmacological evidence for development of DHE as a potential agent against glioma.