Abstract 4440: Using nanocurcumin to treat medulloblastoma and glioblastoma

Abstract

We attempted to treat medulloblastoma and glioblastoma, malignant tumors of the central nervous system, with curcumin, a polyphenolic compound derived from the Indian spice turmeric. Curcumin was delivered in a nanoparticle-encapsulated formulation (nanocurcumin) to increase its solubility and bioavailability. Nanocurcumin caused a dose-dependent decrease in cell growth as measured by MTT in multiple brain cancer cell lines, including the embryonal tumor derived cultures DAOY, D283, and PFSK, and the glioblastoma neurosphere line HSR-GBM1. Notably, doses used in these studies did not cause a comparable inhibition in the growth of NIH 3T3 cells or non-neoplastic human fetal cortical neurospheres. The reductions in viable cell mass observed were associated with a combination of G2/M arrest and apoptotic induction. The proportion of G2/M cells increased between 25% and 106% in the various lines, while the percentage of apoptotic cells increased at least two-fold. Nanocurcumin was also found to reduce the CD133+ stem-like cancer cell population in medulloblastoma and glioblastoma cells. In the primary glioblastoma culture JHH-GBM14, the CD133+ population decreased from 7.7% to 0.6%. In addition, 10uM nanocurcumin suppressed clonogenicity of our brain tumor cell lines by more than 97%. Curcumin has been shown to target multiple pathways in different tumor types. We found that Stat3 activity was reduced by nanocurcumin in the DAOY medulloblastoma cell line, via reductions in phospho-Tyr705 and phospho-Ser727. Nanocurcumin also reduced the expression of Hes 5, one of the target genes in the Notch pathway. However, we did not find significant changes in protein expression of Bcl2, MEK, ERK and Akt following nanocurcumin treatment. In conclusion, our results suggest that nanocurcumin can inhibit malignant brain tumor growth, at least in part due to reduction in Stat activity. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4440.

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