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Inhibitor of Nicotinamide Phosphoribosyltransferase Sensitizes Glioblastoma Cells to Temozolomide via Activating ROSJNK Signaling Pathway
Joint Authors
Feng, Jun
Yan, Peng-Fei
Zhao, Hong-yang
Zhang, Fang-Cheng
Zhao, Wo-Hua
Feng, Min
Source
Issue
Vol. 2016, Issue 2016 (31 Dec. 2016), pp.1-11, 11 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2016-12-20
Country of Publication
Egypt
No. of Pages
11
Main Subjects
Abstract EN
Overcoming temozolomide (TMZ) resistance is a great challenge in glioblastoma (GBM) treatment.
Nicotinamide phosphoribosyltransferase (NAMPT) is a rate-limiting enzyme in the biosynthesis of nicotinamide adenine dinucleotide and has a crucial role in cancer cell metabolism.
In this study, we investigated whether FK866 and CHS828, two specific NAMPT inhibitors, could sensitize GBM cells to TMZ.
Low doses of FK866 and CHS828 (5 nM and 10 nM, resp.) alone did not significantly decrease cell viability in U251-MG and T98 GBM cells.
However, they significantly increased the antitumor action of TMZ in these cells.
In U251-MG cells, administration of NAMPT inhibitors increased the TMZ (100 μM)-induced apoptosis and LDH release from GBM cells.
NAMPT inhibitors remarkably enhanced the activities of caspase-1, caspase-3, and caspase-9.
Moreover, NAMPT inhibitors increased reactive oxygen species (ROS) production and superoxide anion level but reduced the SOD activity and total antioxidative capacity in GBM cells.
Treatment of NAMPT inhibitors increased phosphorylation of c-Jun and JNK.
Administration of JNK inhibitor SP600125 or ROS scavenger tocopherol with TMZ and NAMPT inhibitors substantially attenuated the sensitization of NAMPT inhibitor on TMZ antitumor action.
Our data indicate a potential value of NAMPT inhibitors in combined use with TMZ for GBM treatment.
American Psychological Association (APA)
Feng, Jun& Yan, Peng-Fei& Zhao, Hong-yang& Zhang, Fang-Cheng& Zhao, Wo-Hua& Feng, Min. 2016. Inhibitor of Nicotinamide Phosphoribosyltransferase Sensitizes Glioblastoma Cells to Temozolomide via Activating ROSJNK Signaling Pathway. BioMed Research International،Vol. 2016, no. 2016, pp.1-11.
https://search.emarefa.net/detail/BIM-1096883
Modern Language Association (MLA)
Feng, Jun…[et al.]. Inhibitor of Nicotinamide Phosphoribosyltransferase Sensitizes Glioblastoma Cells to Temozolomide via Activating ROSJNK Signaling Pathway. BioMed Research International No. 2016 (2016), pp.1-11.
https://search.emarefa.net/detail/BIM-1096883
American Medical Association (AMA)
Feng, Jun& Yan, Peng-Fei& Zhao, Hong-yang& Zhang, Fang-Cheng& Zhao, Wo-Hua& Feng, Min. Inhibitor of Nicotinamide Phosphoribosyltransferase Sensitizes Glioblastoma Cells to Temozolomide via Activating ROSJNK Signaling Pathway. BioMed Research International. 2016. Vol. 2016, no. 2016, pp.1-11.
https://search.emarefa.net/detail/BIM-1096883
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1096883