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Plant HDAC inhibitor chrysin arrest cell growth and induce p21(WAF1) by altering chromatin of STAT response element in A375 cells

BACKGROUND: Chrysin and its analogues, belongs to flavonoid family and possess potential anti-tumour activity. The aim of this study is to determine the molecular mechanism by which chrysin controls cell growth and induce apoptosis in A375 cells. METHODS: Effect of chrysin and its analogues on cell...

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Autores principales: Pal-Bhadra, Manika, Ramaiah, M Janaki, Reddy, T Lakshminarayan, Krishnan, Anita, Pushpavalli, SNCVL, Babu, K Suresh, Tiwari, Ashok K, Rao, J Madhusudana, Yadav, Jhillu S, Bhadra, Utpal
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3407000/
https://www.ncbi.nlm.nih.gov/pubmed/22591439
http://dx.doi.org/10.1186/1471-2407-12-180
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author Pal-Bhadra, Manika
Ramaiah, M Janaki
Reddy, T Lakshminarayan
Krishnan, Anita
Pushpavalli, SNCVL
Babu, K Suresh
Tiwari, Ashok K
Rao, J Madhusudana
Yadav, Jhillu S
Bhadra, Utpal
author_facet Pal-Bhadra, Manika
Ramaiah, M Janaki
Reddy, T Lakshminarayan
Krishnan, Anita
Pushpavalli, SNCVL
Babu, K Suresh
Tiwari, Ashok K
Rao, J Madhusudana
Yadav, Jhillu S
Bhadra, Utpal
author_sort Pal-Bhadra, Manika
collection PubMed
description BACKGROUND: Chrysin and its analogues, belongs to flavonoid family and possess potential anti-tumour activity. The aim of this study is to determine the molecular mechanism by which chrysin controls cell growth and induce apoptosis in A375 cells. METHODS: Effect of chrysin and its analogues on cell viability and cell cycle analysis was determined by MTT assay and flowcytometry. A series of Western blots was performed to determine the effect of chrysin on important cell cycle regulatory proteins (Cdk2, cyclin D1, p53, p21, p27). The fluorimetry and calorimetry based assays was conducted for characterization of chrysin as HDAC inhibitor. The changes in histone tail modification such as acetylation and methylation was studied after chrysin treatment was estimated by immuno-fluorescence and western blot analysis. The expression of Bcl-xL, survivin and caspase-3 was estimated in chrysin treated cells. The effect of chrysin on p21 promoter activity was studied by luciferase and ChIP assays. RESULTS: Chrysin cause G1 cell cycle arrest and found to inhibit HDAC-2 and HDAC-8. Chrysin treated cells have shown increase in the levels of H3acK14, H4acK12, H4acK16 and decrease in H3me2K9 methylation. The p21 induction by chrysin treatment was found to be independent of p53 status. The chromatin remodelling at p21(WAF1) promoter induces p21 activity, increased STAT-1 expression and epigenetic modifications that are responsible for ultimate cell cycle arrest and apoptosis. CONCLUSION: Chrysin shows in vitro anti-cancer activity that is correlated with induction of histone hyperacetylation and possible recruitment of STAT-1, 3, 5 proteins at STAT (−692 to −684) region of p21 promoter. Our results also support an unexpected action of chrysin on the chromatin organization of p21(WAF1) promoter through histone methylation and hyper-acetylation. It proposes previously unknown sequence specific chromatin modulations in the STAT responsive elements for regulating cell cycle progression negatively via the induction of the CDK inhibitor p21(WAF1).
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spelling pubmed-34070002012-07-28 Plant HDAC inhibitor chrysin arrest cell growth and induce p21(WAF1) by altering chromatin of STAT response element in A375 cells Pal-Bhadra, Manika Ramaiah, M Janaki Reddy, T Lakshminarayan Krishnan, Anita Pushpavalli, SNCVL Babu, K Suresh Tiwari, Ashok K Rao, J Madhusudana Yadav, Jhillu S Bhadra, Utpal BMC Cancer Research Article BACKGROUND: Chrysin and its analogues, belongs to flavonoid family and possess potential anti-tumour activity. The aim of this study is to determine the molecular mechanism by which chrysin controls cell growth and induce apoptosis in A375 cells. METHODS: Effect of chrysin and its analogues on cell viability and cell cycle analysis was determined by MTT assay and flowcytometry. A series of Western blots was performed to determine the effect of chrysin on important cell cycle regulatory proteins (Cdk2, cyclin D1, p53, p21, p27). The fluorimetry and calorimetry based assays was conducted for characterization of chrysin as HDAC inhibitor. The changes in histone tail modification such as acetylation and methylation was studied after chrysin treatment was estimated by immuno-fluorescence and western blot analysis. The expression of Bcl-xL, survivin and caspase-3 was estimated in chrysin treated cells. The effect of chrysin on p21 promoter activity was studied by luciferase and ChIP assays. RESULTS: Chrysin cause G1 cell cycle arrest and found to inhibit HDAC-2 and HDAC-8. Chrysin treated cells have shown increase in the levels of H3acK14, H4acK12, H4acK16 and decrease in H3me2K9 methylation. The p21 induction by chrysin treatment was found to be independent of p53 status. The chromatin remodelling at p21(WAF1) promoter induces p21 activity, increased STAT-1 expression and epigenetic modifications that are responsible for ultimate cell cycle arrest and apoptosis. CONCLUSION: Chrysin shows in vitro anti-cancer activity that is correlated with induction of histone hyperacetylation and possible recruitment of STAT-1, 3, 5 proteins at STAT (−692 to −684) region of p21 promoter. Our results also support an unexpected action of chrysin on the chromatin organization of p21(WAF1) promoter through histone methylation and hyper-acetylation. It proposes previously unknown sequence specific chromatin modulations in the STAT responsive elements for regulating cell cycle progression negatively via the induction of the CDK inhibitor p21(WAF1). BioMed Central 2012-05-16 /pmc/articles/PMC3407000/ /pubmed/22591439 http://dx.doi.org/10.1186/1471-2407-12-180 Text en Copyright ©2012 Pal‒Bhadra et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Pal-Bhadra, Manika
Ramaiah, M Janaki
Reddy, T Lakshminarayan
Krishnan, Anita
Pushpavalli, SNCVL
Babu, K Suresh
Tiwari, Ashok K
Rao, J Madhusudana
Yadav, Jhillu S
Bhadra, Utpal
Plant HDAC inhibitor chrysin arrest cell growth and induce p21(WAF1) by altering chromatin of STAT response element in A375 cells
title Plant HDAC inhibitor chrysin arrest cell growth and induce p21(WAF1) by altering chromatin of STAT response element in A375 cells
title_full Plant HDAC inhibitor chrysin arrest cell growth and induce p21(WAF1) by altering chromatin of STAT response element in A375 cells
title_fullStr Plant HDAC inhibitor chrysin arrest cell growth and induce p21(WAF1) by altering chromatin of STAT response element in A375 cells
title_full_unstemmed Plant HDAC inhibitor chrysin arrest cell growth and induce p21(WAF1) by altering chromatin of STAT response element in A375 cells
title_short Plant HDAC inhibitor chrysin arrest cell growth and induce p21(WAF1) by altering chromatin of STAT response element in A375 cells
title_sort plant hdac inhibitor chrysin arrest cell growth and induce p21(waf1) by altering chromatin of stat response element in a375 cells
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3407000/
https://www.ncbi.nlm.nih.gov/pubmed/22591439
http://dx.doi.org/10.1186/1471-2407-12-180
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