Curcumin Regulates Low-Linear Energy Transfer {gamma}-Radiation-Induced NF{kappa}B-Dependent Telomerase Activity in Human Neuroblastoma Cells
- Department of Radiation Oncology, University of Oklahoma Health Sciences Center, Oklahoma City, OK (United States)
- Department of Otolaryngology, Head and Neck Surgery, University of Texas Health Sciences Center at San Antonio, San Antonio, TX (United States)
Purpose: We recently reported that curcumin attenuates ionizing radiation (IR)-induced survival signaling and proliferation in human neuroblastoma cells. Also, in the endothelial system, we have demonstrated that NF{kappa}B regulates IR-induced telomerase activity (TA). Accordingly, we investigated the effect of curcumin in inhibiting IR-induced NF{kappa}B-dependent hTERT transcription, TA, and cell survival in neuroblastoma cells. Methods and Materials: SK-N-MC or SH-SY5Y cells exposed to IR and treated with curcumin (10-100 nM) with or without IR were harvested after 1 h through 24 h. NF{kappa}B-dependent regulation was investigated either by luciferase reporter assays using pNF{kappa}B-, pGL3-354-, pGL3-347-, or pUSE-I{kappa}B{alpha}-Luc, p50/p65, or RelA siRNA-transfected cells. NF{kappa}B activity was analyzed using an electrophoretic mobility shift assay and hTERT expression using the quantitative polymerase chain reaction. TA was determined using the telomerase repeat amplification protocol assay and cell survival using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltertrazolium bromide and clonogenic assay. Results: Curcumin profoundly inhibited IR-induced NF{kappa}B. Consequently, curcumin significantly inhibited IR-induced TA and hTERT mRNA at all points investigated. Furthermore, IR-induced TA is regulated at the transcriptional level by triggering telomerase reverse transcriptase (TERT) promoter activation. Moreover, NF{kappa}B becomes functionally activated after IR and mediates TA upregulation by binding to the {kappa}B-binding region in the promoter region of the TERT gene. Consistently, elimination of the NF{kappa}B-recognition site on the telomerase promoter or inhibition of NF{kappa}B by the I{kappa}B{alpha} mutant compromises IR-induced telomerase promoter activation. Significantly, curcumin inhibited IR-induced TERT transcription. Consequently, curcumin inhibited hTERT mRNA and TA in NF{kappa}B overexpressed cells. Furthermore, curcumin enhanced the IR-induced inhibition of cell survival. Conclusions: These results strongly suggest that curcumin inhibits IR-induced TA in an NF{kappa}B dependent manner in human neuroblastoma cells.
- OSTI ID:
- 21499722
- Journal Information:
- International Journal of Radiation Oncology, Biology and Physics, Vol. 79, Issue 4; Other Information: DOI: 10.1016/j.ijrobp.2010.10.058; PII: S0360-3016(10)03559-5; Copyright (c) 2011 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; ISSN 0360-3016
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
CURCUMIN
GAMMA RADIATION
INHIBITION
LET
LUCIFERASE
MESSENGER-RNA
POLYMERASE CHAIN REACTION
PROMOTERS
TRANSCRIPTION FACTORS
TUMOR CELLS
ANIMAL CELLS
AROMATICS
DYES
ELECTROMAGNETIC RADIATION
ENERGY TRANSFER
ENZYMES
ETHERS
GENE AMPLIFICATION
HYDROXY COMPOUNDS
IONIZING RADIATIONS
KETONES
NUCLEIC ACIDS
ORGANIC COMPOUNDS
ORGANIC OXYGEN COMPOUNDS
OXIDASES
OXIDOREDUCTASES
PHENOLS
POLYPHENOLS
PROTEINS
RADIATIONS
RNA