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  -