Publication: NSAID-activated gene-1 as a molecular target for capsaicin-induced apoptosis through a novel molecular mechanism involving GSK3β, C/EBPβ and ATF3
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Issued Date
2010
Resource Type
File Type
application/pdf
ISSN
1433334
Other identifier(s)
2-s2.0-77950896712
Rights Holder(s)
Scopus
Bibliographic Citation
Carcinogenesis. Vol 31, No.4 (2010), p.719-728
Suggested Citation
Lee S.-H., Krisanapun C., Baek S.J. NSAID-activated gene-1 as a molecular target for capsaicin-induced apoptosis through a novel molecular mechanism involving GSK3β, C/EBPβ and ATF3. Carcinogenesis. Vol 31, No.4 (2010), p.719-728. doi:10.1093/carcin/bgq016 Retrieved from: https://hdl.handle.net/20.500.14740/7631
Author(s)
Abstract
Capsaicin, a natural product of the Capsicum species of red peppers, is known to induce apoptosis and suppress growth. Nonsteroidal anti-inflammatory drug-activated gene-1 (NAG-1) is a cytokine associated with pro-apoptotic and antitumorigenic property in colorectal and lung cancer. Our data demonstrate that capsaicin leads to induction of apoptosis and up-regulates NAG-1 gene expression at the transcriptional level. Overexpression of CCAAT/enhancer binding protein β (C/EBPβ) caused a significant increase of basal and capsaicin-induced NAG-1 promoter activity. We subsequently identified C/EBPβ binding sites in the NAG-1 promoter responsible for capsaicin-induced NAG-1 transactivation. Electrophoretic mobility shift assay and chromatin immunoprecipitation assay confirmed binding of C/EBPβ to the NAG-1 promoter. Capsaicin treatment resulted in an increase of phosphorylated serine/threonine residues on C/EBPβ, and the immunoprecipitation study showed that capsaicin enhanced binding of C/EBPβ with glycogen synthase kinase 3β (GSK3β) and activating transcription factor 3 (ATF3). The phosphorylation and interaction of C/EBPβ with GSK3β and ATF3 are decreased by the inhibition of the GSK3β and Protein Kinase C pathways. Knockdown of C/EBPβ, GSK3β or ATF3 ameliorates NAG-1 expression induced by capsaicin treatment. These data indicate that C/EBPβ phosphorylation through GSK3β may mediate capsaicin-induced expression of NAG-1 and apoptosis through cooperation with ATF3 in human colorectal cancer cells. © The Author 2010. Published by Oxford University Press. All rights reserved. For Permissions, please email: [email protected].
Subject(s)
Activating transcription factor 3
Capsaicin
CCAAT enhancer binding protein beta
Glycogen synthase kinase 3beta
Nonsteroid antiinflammatory drug activated gene 1 protein
Protein kinase C
Unclassified drug
Activating transcription factor 3
ATF3 protein, human
CCAAT enhancer binding protein beta
GDF15 protein, human
Glycogen synthase kinase 3
Glycogen synthase kinase 3 beta
Growth differentiation factor 15
Protein kinase C
Retinoic acid receptor
Retinoic acid receptor alpha
Antineoplastic activity
Apoptosis
Article
Binding site
Cancer cell culture
Cancer inhibition
Colorectal cancer
Controlled study
Drug targeting
Gene expression regulation
Human
Human cell
Priority journal
Promoter region
Protein phosphorylation
Protein protein interaction
Signal transduction
Transactivation
Upregulation
Cell strain HCT116
Cell strain HT29
Colorectal tumor
Drug effect
Genetics
Pathology
Phosphorylation
Physiology
Activating Transcription Factor 3
Apoptosis
Capsaicin
CCAAT-Enhancer-Binding Protein-beta
Colorectal Neoplasms
Glycogen Synthase Kinase 3
Growth Differentiation Factor 15
HCT116 Cells
HT29 Cells
Humans
Phosphorylation
Promoter Regions, Genetic
Protein Kinase C
Receptors, Retinoic Acid
Signal Transduction
Capsaicin
CCAAT enhancer binding protein beta
Glycogen synthase kinase 3beta
Nonsteroid antiinflammatory drug activated gene 1 protein
Protein kinase C
Unclassified drug
Activating transcription factor 3
ATF3 protein, human
CCAAT enhancer binding protein beta
GDF15 protein, human
Glycogen synthase kinase 3
Glycogen synthase kinase 3 beta
Growth differentiation factor 15
Protein kinase C
Retinoic acid receptor
Retinoic acid receptor alpha
Antineoplastic activity
Apoptosis
Article
Binding site
Cancer cell culture
Cancer inhibition
Colorectal cancer
Controlled study
Drug targeting
Gene expression regulation
Human
Human cell
Priority journal
Promoter region
Protein phosphorylation
Protein protein interaction
Signal transduction
Transactivation
Upregulation
Cell strain HCT116
Cell strain HT29
Colorectal tumor
Drug effect
Genetics
Pathology
Phosphorylation
Physiology
Activating Transcription Factor 3
Apoptosis
Capsaicin
CCAAT-Enhancer-Binding Protein-beta
Colorectal Neoplasms
Glycogen Synthase Kinase 3
Growth Differentiation Factor 15
HCT116 Cells
HT29 Cells
Humans
Phosphorylation
Promoter Regions, Genetic
Protein Kinase C
Receptors, Retinoic Acid
Signal Transduction