Abstract
BackgroundGlioblastoma Multiforme (GBM) is the most common and lethal form of primary brain tumor in adults. Following standard treatment of surgery, radiation and chemotherapy, patients are expected to survive 12–14 months. Theorized cause of disease recurrence in these patients is tumor cell repopulation through the proliferation of treatment-resistant cancer stem cells. Current research has revealed curcumin, the principal ingredient in turmeric, can modulate multiple signaling pathways important for cancer stem cell self-renewal and survival.MethodsFollowing resection, tumor specimens were dissociated and glioblastoma stem cells (GSCs) were propagated in neurosphere media and characterized via immunocytochemistry. Cell viability was determined with MTS assay. GSC proliferation, sphere forming and colony forming assays were conducted through standard counting methods. Reactive oxygen species (ROS) production was examined using the fluorescent molecular probe CM-H2DCFA. Effects on cell signaling pathways were elucidated by western blot.ResultsWe evaluate the effects of curcumin on patient-derived GSC lines. We demonstrate a curcumin-induced dose-dependent decrease in GSC viability with an approximate IC50 of 25 μM. Treatment with sub-toxic levels (2.5 μM) of curcumin significantly decreased GSC proliferation, sphere forming ability and colony forming potential. Curcumin induced ROS, promoted MAPK pathway activation, downregulated STAT3 activity and IAP family members. Inhibition of ROS with the antioxidant N-acetylcysteine reversed these effects indicating a ROS dependent mechanism.ConclusionsDiscoveries made in this investigation may lead to a non-toxic intervention designed to prevent recurrence in glioblastoma by targeting glioblastoma stem cells.
Highlights
Glioblastoma Multiforme (GBM) is the most common and lethal form of primary brain tumor in adults
Since there is no definitive marker for GBM stem cells, we examined the expression of multiple putative cancer stem cell markers by immunocytochemistry [40,41,42,43,44,45]
Our results demonstrate that temozolomide had no significant effect on the viability of these GBM cell lines compared to nontreated controls (Fig. 1b)
Summary
Glioblastoma Multiforme (GBM) is the most common and lethal form of primary brain tumor in adults. Theorized cause of disease recurrence in these patients is tumor cell repopulation through the proliferation of treatment-resistant cancer stem cells. The lack of improvement in survival rates of glioblastoma has led to the identification of novel therapeutic mechanisms such as targeting cancer stem cells (CSCs), known as tumor initiating cells or cancer stem-like cells, in order to eradicate this lethal disease. The unique qualities of CSCs allow them to evade the chemotherapy and radiation that destroys the bulk of the tumor, eventually leading to the recurrence of disease. This idea has led researchers in search for targeted therapies that will eliminate CSCs and prevent the relapse of cancer
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