title: Migration-prone glioma cells show curcumin resistance associated with enhanced expression of miR-21 and invasion/anti-apoptosis-related proteins.
abstract: In study, the expression patterns and functional differences between an original glioma cell population (U251 and U87) and sublines (U251-P10, U87-P10) that were selected to be migration-prone were investigated. The expressions levels of VEGF and intracellular adhesion molecule-1 (ICAM-1) were increased in the migration-prone sublines as well as in samples from patients with high-grade glioma when compared to those with low-grade glioma. In addition, cells of the migration-prone sublines showed increased expression of the oncogenic microRNA. miR-21, which was also associated with more advanced clinical pathological stages in the patient tissue specimens. Treatment of U251 cells with an miR-21 mimic dramatically enhanced the migratory activity and expression of anti-apoptotic proteins. Furthermore, treatment with curcumin decreased the miR-21 level and anti-apoptotic protein expression, and increased the expression of pro-apoptosis proteins and microtubule-associated protein light chain 3-II (LC3-II) in U251 cells. The migration-prone sublines showed decreased induction of cell death markers in response to curcumin treatment. Finally, U251-P10 cells showed resistance against curcumin treatment. These results suggest that miR-21 is associated with regulation of the migratory ability and survival in human glioma cells. These findings suggest novel mechanisms of malignancy and new potential combinatorial strategies for the management of malignant glioma.
authors.affiliation: Department of Cell and Tissue Engineering, Changhua Christian Hospital, Changhua, Taiwan.
authors.forename: Wei-Lan
authors.initials: WL
authors.lastname: Yeh
authors.affiliation: Graduate Institute of Neural and Cognitive Sciences, China Medical University, Taichung, Taiwan.
authors.forename: Hsiao-Yun
authors.initials: HY
authors.lastname: Lin
authors.affiliation: Department of Neurosurgery, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan, Taiwan.
authors.forename: Chiung-Yin
authors.initials: CY
authors.lastname: Huang
authors.affiliation: School of Medicine, Tzu Chi University, Hualien, Taiwan.|Department of Neurosurgery, Taichung Tzu Chi General Hospital, Taichung, Taiwan.
authors.forename: Bor-Ren
authors.initials: BR
authors.lastname: Huang
authors.affiliation: Department of Physiology, School of Medicine, China Medical University, Taichung, Taiwan.
authors.forename: Chingju
authors.initials: C
authors.lastname: Lin
authors.affiliation: Graduate Institute of Neural and Cognitive Sciences, China Medical University, Taichung, Taiwan.|Department of Photonics and Communication Engineering, Asia University, Taichung, Taiwan.
authors.forename: Dah-Yuu
authors.initials: DY
authors.lastname: Lu
authors.affiliation: Department of Neurosurgery, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan, Taiwan.
authors.forename: Kuo-Chen
authors.initials: KC
authors.lastname: Wei
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D003474:Curcumin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D005910:Glioma / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007124:Immunoenzyme Techniques; D035683:MicroRNAs / Q000235:genetics*; D009361:Neoplasm Invasiveness; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; C000595707:BCL2 protein, human; C524940:MIRN21 microRNA, human; D035683:MicroRNAs; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D003474:Curcumin
keywords: curcumin; death receptor; glioma; miR-21; migration