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Inhibition of p300 lysine acetyltransferase activity by luteolin reduces tumor growth in head and neck squamous cell carcinoma (HNSCC) xenograft mouse model

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 acetylatio...

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Autores principales: Selvi, Ruthrotha B., Swaminathan, Amrutha, Chatterjee, Snehajyoti, Shanmugam, Muthu K., Li, Feng, Ramakrishnan, Gowsica B., Siveen, Kodappully Sivaraman, Chinnathambi, Arunachalam, Zayed, M. Emam, Alharbi, Sulaiman Ali, Basha, Jeelan, Bhat, Akshay, Vasudevan, Madavan, Dharmarajan, Arunasalam, Sethi, Gautam, Kundu, Tapas K.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4791268/
https://www.ncbi.nlm.nih.gov/pubmed/26517526
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author Selvi, Ruthrotha B.
Swaminathan, Amrutha
Chatterjee, Snehajyoti
Shanmugam, Muthu K.
Li, Feng
Ramakrishnan, Gowsica B.
Siveen, Kodappully Sivaraman
Chinnathambi, Arunachalam
Zayed, M. Emam
Alharbi, Sulaiman Ali
Basha, Jeelan
Bhat, Akshay
Vasudevan, Madavan
Dharmarajan, Arunasalam
Sethi, Gautam
Kundu, Tapas K.
author_facet Selvi, Ruthrotha B.
Swaminathan, Amrutha
Chatterjee, Snehajyoti
Shanmugam, Muthu K.
Li, Feng
Ramakrishnan, Gowsica B.
Siveen, Kodappully Sivaraman
Chinnathambi, Arunachalam
Zayed, M. Emam
Alharbi, Sulaiman Ali
Basha, Jeelan
Bhat, Akshay
Vasudevan, Madavan
Dharmarajan, Arunasalam
Sethi, Gautam
Kundu, Tapas K.
author_sort Selvi, Ruthrotha B.
collection PubMed
description 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 down-regulation 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.
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spelling pubmed-47912682016-03-28 Inhibition of p300 lysine acetyltransferase activity by luteolin reduces tumor growth in head and neck squamous cell carcinoma (HNSCC) xenograft mouse model Selvi, Ruthrotha B. Swaminathan, Amrutha Chatterjee, Snehajyoti Shanmugam, Muthu K. Li, Feng Ramakrishnan, Gowsica B. Siveen, Kodappully Sivaraman Chinnathambi, Arunachalam Zayed, M. Emam Alharbi, Sulaiman Ali Basha, Jeelan Bhat, Akshay Vasudevan, Madavan Dharmarajan, Arunasalam Sethi, Gautam Kundu, Tapas K. Oncotarget Research Paper 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 down-regulation 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. Impact Journals LLC 2015-10-26 /pmc/articles/PMC4791268/ /pubmed/26517526 Text en Copyright: © 2015 Selvi et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Selvi, Ruthrotha B.
Swaminathan, Amrutha
Chatterjee, Snehajyoti
Shanmugam, Muthu K.
Li, Feng
Ramakrishnan, Gowsica B.
Siveen, Kodappully Sivaraman
Chinnathambi, Arunachalam
Zayed, M. Emam
Alharbi, Sulaiman Ali
Basha, Jeelan
Bhat, Akshay
Vasudevan, Madavan
Dharmarajan, Arunasalam
Sethi, Gautam
Kundu, Tapas K.
Inhibition of p300 lysine acetyltransferase activity by luteolin reduces tumor growth in head and neck squamous cell carcinoma (HNSCC) xenograft mouse model
title Inhibition of p300 lysine acetyltransferase activity by luteolin reduces tumor growth in head and neck squamous cell carcinoma (HNSCC) xenograft mouse model
title_full Inhibition of p300 lysine acetyltransferase activity by luteolin reduces tumor growth in head and neck squamous cell carcinoma (HNSCC) xenograft mouse model
title_fullStr Inhibition of p300 lysine acetyltransferase activity by luteolin reduces tumor growth in head and neck squamous cell carcinoma (HNSCC) xenograft mouse model
title_full_unstemmed Inhibition of p300 lysine acetyltransferase activity by luteolin reduces tumor growth in head and neck squamous cell carcinoma (HNSCC) xenograft mouse model
title_short Inhibition of p300 lysine acetyltransferase activity by luteolin reduces tumor growth in head and neck squamous cell carcinoma (HNSCC) xenograft mouse model
title_sort inhibition of p300 lysine acetyltransferase activity by luteolin reduces tumor growth in head and neck squamous cell carcinoma (hnscc) xenograft mouse model
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4791268/
https://www.ncbi.nlm.nih.gov/pubmed/26517526
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