Abstract
BackgroundNew drugs are constantly sought after to improve the survival of patients with malignant gliomas. The ideal substance would selectively target tumor cells without eliciting toxic side effects. Here, we report on the anti-proliferative, anti-migratory, and anti-invasive properties of the natural, nontoxic compound Curcumin observed in five human glioblastoma (GBM) cell lines in vitro.MethodsWe used monolayer wound healing assays, modified Boyden chamber trans-well assays, and cell growth assays to quantify cell migration, invasion, and proliferation in the absence or presence of Curcumin at various concentrations. Levels of the transcription factor phospho-STAT3, a potential target of Curcumin, were determined by sandwich-ELISA. Subsequent effects on transcription of genes regulating the cell cycle were analyzed by quantitative real-time PCR. Effects on apoptosis were determined by caspase assays.ResultsCurcumin potently inhibited GBM cell proliferation as well as migration and invasion in all cell lines contingent on dose. Simultaneously, levels of the biologically active phospho-STAT3 were decreased and correlated with reduced transcription of the cell cycle regulating gene c-Myc and proliferation marking Ki-67, pointing to a potential mechanism by which Curcumin slows tumor growth.ConclusionsCurcumin is part of the diet of millions of people every day and is without known toxic side effects. Our data show that Curcumin bears anti-proliferative, anti-migratory, and anti-invasive properties against GBM cells in vitro. These results warrant further in vivo analyses and indicate a potential role of Curcumin in the treatment of malignant gliomas.
Highlights
New drugs are constantly sought after to improve the survival of patients with malignant gliomas
Sandwich ELISA To elucidate the potential mechanism of action, we examined the effect of Curcumin treatment on the phosphorylation status of the transcription factor STAT3 employing a sandwich-ELISA kit (PathScan® Phospho-Stat3 (Tyr705) Sandwich ELISA Antibody Pair #7146; Cell Signaling Technology Inc., Danvers, MA) according to the manufacturer’s advice
Curcumin is a potent inhibitor of GBM proliferation To examine whether treatment with Curcumin influences tumor cell proliferation, we employed methyl-thiazolyl tetrazolium bromide (MTT) assays
Summary
New drugs are constantly sought after to improve the survival of patients with malignant gliomas. We report on the anti-proliferative, anti-migratory, and anti-invasive properties of the natural, nontoxic compound Curcumin observed in five human glioblastoma (GBM) cell lines in vitro. The introduction of temozolomide treatment in addition to radiotherapy after surgical resection has improved survival in patients with glioblastoma (GBM), tumor recurrence is inevitable [1,2]. A subpopulation of patients (with a methylated O(6)-methylguanine-DNA methyltransferase (MGMT) gene promoter) may benefit from dose-intensified temozolomide treatment with added lomustine in terms of overall survival, at the cost of increased toxicity [4]. Recent preclinical as well as first clinical reports have indicated that Curcumin may be effective in the treatment of various cancers [7,8,9,10]. The underlying mechanisms of this efficacy are still under investigation, but recently an association with the JAK/STAT3 pathway has been proposed [11]
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