TY - JOUR AU - Gersey, Z.C. AU - Rodriguez, G.A. AU - Barbarite, E. AU - Sanchez, A. AU - Walters, W.M. AU - Ohaeto, K.C. AU - Komotar, R.J. AU - Graham, R.M. PY - 2017// TI - Curcumin decreases malignant characteristics of glioblastoma stem cells via induction of reactive oxygen species T2 - BMC Cancer JO - BMC Cancer SP - 99 VL - 17 IS - 1 KW - Acetylcysteine/pharmacology KW - Adult KW - Antineoplastic Agents/*pharmacology KW - Cell Proliferation/drug effects KW - Cell Survival/drug effects KW - Curcumin/*pharmacology KW - Drug Resistance KW - Neoplasm KW - Drug Screening Assays KW - Antitumor KW - Free Radical Scavengers KW - Glioblastoma/drug therapy/pathology KW - Humans KW - Inhibitor of Apoptosis Proteins/metabolism KW - Inhibitory Concentration 50 KW - Mitogen-Activated Protein Kinases/metabolism KW - Neoplastic Stem Cells/*drug effects KW - Oxidative Stress KW - Reactive Oxygen Species/*metabolism KW - STAT3 Transcription Factor/metabolism KW - Tumor Cells KW - Cultured KW - Brain tumor KW - Curcumin KW - Glioblastoma KW - Natural product KW - Reactive oxygen species KW - Stat3 KW - Stem cell AB - BACKGROUND: Glioblastoma 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. METHODS: Following 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. RESULTS: We 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 muM. Treatment with sub-toxic levels (2.5 muM) 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. CONCLUSIONS: Discoveries made in this investigation may lead to a non-toxic intervention designed to prevent recurrence in glioblastoma by targeting glioblastoma stem cells. SN - 1471-2407 UR - http://www.ncbi.nlm.nih.gov/pubmed/28160777 UR - PM:28160777 N1 - PMID:28160777 ID - Gersey_etal2017 ER -