Please use this identifier to cite or link to this item: https://doi.org/10.18632/oncotarget.6245
Title: Inhibition of p300 Lysine Acetyltransferase activity by Luteolin reduces tumor growth in head and neck squamous cell carcinoma (HNSCC) xenograft mouse model
Authors: Selvi, R.B
Swaminathan, A
Chatterjee, S
Shanmugam, M.K 
Li, F 
Ramakrishnan, G.B
Siveen, K.S 
Chinnathambi, A
Emam Zayed, M
Alharbi, S.A
Basha, J
Bhat, A
Vasudevan, M
Dharmarajan, A
Sethi, G 
Kundu, T.K
Keywords: acetyl coenzyme A
E1A associated p300 protein
histone
luteolin
microRNA
microRNA 135a
microRNA 195
microRNA 215
microRNA let7C
protein p53
unclassified drug
antineoplastic agent
histone acetyltransferase PCAF
luteolin
lysine
p300-CBP-associated factor
transcriptome
animal experiment
animal model
animal tissue
antineoplastic activity
Article
binding competition
cancer inhibition
cell cycle arrest
chromatin immunoprecipitation
controlled study
down regulation
drug binding site
drug efficacy
enzyme activity
enzyme inhibition
gene expression profiling
gene expression regulation
gene ontology
head and neck squamous cell carcinoma
histone acetylation
human
human cell
migration inhibition
mouse
mouse model
nonhuman
promoter region
RNA processing
treatment duration
tumor xenograft
animal
cell proliferation
DNA microarray
drug effects
drug screening
flow cytometry
head and neck tumor
immunoblotting
immunohistochemistry
metabolism
molecular docking
pathology
squamous cell carcinoma
Animals
Antineoplastic Agents
Carcinoma, Squamous Cell
Cell Proliferation
Chromatin Immunoprecipitation
Flow Cytometry
Head and Neck Neoplasms
Humans
Immunoblotting
Immunohistochemistry
Luteolin
Lysine
Mice
Molecular Docking Simulation
Oligonucleotide Array Sequence Analysis
p300-CBP Transcription Factors
Transcriptome
Xenograft Model Antitumor Assays
Issue Date: 2015
Publisher: Impact Journals LLC
Citation: Selvi, R.B, Swaminathan, A, Chatterjee, S, Shanmugam, M.K, Li, F, Ramakrishnan, G.B, Siveen, K.S, Chinnathambi, A, Emam Zayed, M, Alharbi, S.A, Basha, J, Bhat, A, Vasudevan, M, Dharmarajan, A, Sethi, G, Kundu, T.K (2015). Inhibition of p300 Lysine Acetyltransferase activity by Luteolin reduces tumor growth in head and neck squamous cell carcinoma (HNSCC) xenograft mouse model. Oncotarget 6 (41) : 43806-43818. ScholarBank@NUS Repository. https://doi.org/10.18632/oncotarget.6245
Abstract: Chromatin acetylation is attributed with distinct functional relevance with respect to gene expression in normal and diseased conditions thereby leading to a topical interest in the concept of epigenetic modulators and therapy. We report here the identification and characterization of the acetylation inhibitory potential of an important dietary flavonoid, luteolin. Luteolin was found to inhibit p300 acetyltransferase with competitive binding to the acetyl CoA binding site. Luteolin treatment in a xenografted tumor model of head and neck squamous cell carcinoma (HNSCC), led to a dramatic reduction in tumor growth within 4 weeks corresponding to a decrease in histone acetylation. Cells treated with luteolin exhibit cell cycle arrest and decreased cell migration. Luteolin treatment led to an alteration in gene expression and miRNA profile including up-regulation of p53 induced miR-195/215, let7C; potentially translating into a tumor suppressor function. It also led to downregulation of oncomiRNAs such as miR-135a, thereby reflecting global changes in the microRNA network. Furthermore, a direct correlation between the inhibition of histone acetylation and gene expression was established using chromatin immunoprecipitation on promoters of differentially expressed genes. A network of dysregulated genes and miRNAs was mapped along with the gene ontology categories, and the effects of luteolin were observed to be potentially at multiple levels: at the level of gene expression, miRNA expression and miRNA processing.
Source Title: Oncotarget
URI: https://scholarbank.nus.edu.sg/handle/10635/175520
ISSN: 19492553
DOI: 10.18632/oncotarget.6245
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