Curcumin decreases malignant characteristics of glioblastoma stem cells via induction of reactive oxygen species

BMC Cancer

Research Article

Eric Barbarite¹  Winston M. Walters¹  Zachary C. Gersey¹  Gregor A. Rodriguez¹  Ricardo J. Komotar¹  Kelechi C. Ohaeto¹  Anthony Sanchez¹  Regina M. Graham² 

[1] Department of Neurosurgery, University of Miami Miller School of Medicine, Miami, Florida, USA;Department of Neurosurgery, University of Miami Miller School of Medicine, Miami, Florida, USA;Department of Neurological Surgery, University of Miami Brain Tumor Initiative (UMBTI) Research Laboratory, Lois Pope LIFE Center, 2nd Floor, 1095 NW 14th Terrace, 33136, Miami, Florida, USA;

关键词: Glioblastoma;    Stem cell;    STAT3;    Curcumin;    Reactive oxygen species;    Brain tumor;    Natural product;   

DOI  :  10.1186/s12885-017-3058-2

 received in 2016-10-20, accepted in 2017-01-11,  发布年份 2017

来源: Springer

【 摘 要 】

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.

【 授权许可】

CC BY   
© The Author(s). 2017