Abstract B171: Involvement of Akt/NF-κ B pathway in antitumor effect of parthenolide on glioblastoma cells.

Abstract

Abstract Background: Glioblastoma is the most common and aggressive form of malignant glioma and is very difficult to treat. Controlling glioblastoma cell invasion and angiogenesis is essential to improve the prognosis of glioblastoma patients. Constitutive activation of Nuclear factor-κB (NF-κB) is crucial for tumor progression. Inhibition of NF-κB may be an important pharmacological target for the control of tumor progression. Our study aimed to evaluate the antitumour effects of parthenolide, NF-κB inhibitor, on two human glioma cell lines (U87MG, U373) and the molecular mechanisms underlying these effects. Methods: The anti-invasive effect of parthenolide was analysed by an in vitro invasion assay. An in vitro angiogenesis assay was also performed. In vitro growth inhibition of glioma cells by parthenolide was determined by the MTT assay. The effect of parthenolide on an orthotropic implantation model using athymic mice was also evaluated. Results: Parthenolide suppressed the proliferation of glioblastoma cells. Parthenolide also suppressed both the invasion of glioblastoma cells and tumor-induced angiogenesis. Molecular-based studies demonstrated that parthenolide suppressed gene and protein expression of angiogenic factors. Furthermore, parthenolide reduced the phosphorylation of Akt and activated mitochondrial cascade, suggesting that the antitumor effect of parthenolide may be mediated by the inhibition of the Akt signal and the activation of apoptotic proteins. An in vivo intracerebral human glioblastoma xenograft mouse model demonstrated that parthenolide suppressed neovascularity and tumor growth. Conclusions: The results of the present study suggest that parthenolide may be a new therapeutic agent for glioblastomas. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2011 Nov 12-16; San Francisco, CA. Philadelphia (PA): AACR; Mol Cancer Ther 2011;10(11 Suppl):Abstract nr B171.