Structural insight for the recognition of G-quadruplex structure at human c-myc promoter sequence by flavonoid Quercetin

Abstract Small molecule ligands that could stabilize G-quadruplex structure formed at the promoter region of human c-myc oncogene will regulate its expression in cancer cells. Flavonoids, a group of naturally available small molecule, have been known for their various promising effects on human heal...

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Autores principales:	Arpita Tawani, Subodh Kumar Mishra, Amit Kumar
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/d2ba3ee4825e4473966e93502f33a65e
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spelling	oai:doaj.org-article:d2ba3ee4825e4473966e93502f33a65e2021-12-02T12:32:26ZStructural insight for the recognition of G-quadruplex structure at human c-myc promoter sequence by flavonoid Quercetin10.1038/s41598-017-03906-32045-2322https://doaj.org/article/d2ba3ee4825e4473966e93502f33a65e2017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-03906-3https://doaj.org/toc/2045-2322Abstract Small molecule ligands that could stabilize G-quadruplex structure formed at the promoter region of human c-myc oncogene will regulate its expression in cancer cells. Flavonoids, a group of naturally available small molecule, have been known for their various promising effects on human health. In present study, we have performed detailed biophysical studies for the interaction of human c-myc G-quadruplex DNA with nine representative flavonoids: Luteolin, Quercetin, Rutin, Genistein, Kaempferol, Puerarin, Hesperidin, Myricetin and Daidzein. We found by using fluorescence titration that Quercetin interacts with c-myc G-quadruplex DNA sequence Pu24T with highest affinity. This interaction was further explored by using NMR spectroscopy and we have derived the first solution structure for the complex formed between Quercetin and biologically significant c-myc promoter DNA sequence forming G-quadruplex structure. In present solution structure, Quercetin stacks at 5′ and 3′ G-tetrads of Pu24T G-quadruplex structure and stabilize it via π-π stacking interactions. Furthermore, in vitro studies on HeLa cells suggested that Quercetin induces apoptosis-mediated cell death and down-regulated c-myc gene expression. This study emphasizes the potential of flavonoids as a promising candidate for targeting c-myc promoter region and thus, could act as a potential anti-cancer agent.Arpita TawaniSubodh Kumar MishraAmit KumarNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-13 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Arpita Tawani Subodh Kumar Mishra Amit Kumar Structural insight for the recognition of G-quadruplex structure at human c-myc promoter sequence by flavonoid Quercetin
description	Abstract Small molecule ligands that could stabilize G-quadruplex structure formed at the promoter region of human c-myc oncogene will regulate its expression in cancer cells. Flavonoids, a group of naturally available small molecule, have been known for their various promising effects on human health. In present study, we have performed detailed biophysical studies for the interaction of human c-myc G-quadruplex DNA with nine representative flavonoids: Luteolin, Quercetin, Rutin, Genistein, Kaempferol, Puerarin, Hesperidin, Myricetin and Daidzein. We found by using fluorescence titration that Quercetin interacts with c-myc G-quadruplex DNA sequence Pu24T with highest affinity. This interaction was further explored by using NMR spectroscopy and we have derived the first solution structure for the complex formed between Quercetin and biologically significant c-myc promoter DNA sequence forming G-quadruplex structure. In present solution structure, Quercetin stacks at 5′ and 3′ G-tetrads of Pu24T G-quadruplex structure and stabilize it via π-π stacking interactions. Furthermore, in vitro studies on HeLa cells suggested that Quercetin induces apoptosis-mediated cell death and down-regulated c-myc gene expression. This study emphasizes the potential of flavonoids as a promising candidate for targeting c-myc promoter region and thus, could act as a potential anti-cancer agent.
format	article
author	Arpita Tawani Subodh Kumar Mishra Amit Kumar
author_facet	Arpita Tawani Subodh Kumar Mishra Amit Kumar
author_sort	Arpita Tawani
title	Structural insight for the recognition of G-quadruplex structure at human c-myc promoter sequence by flavonoid Quercetin
title_short	Structural insight for the recognition of G-quadruplex structure at human c-myc promoter sequence by flavonoid Quercetin
title_full	Structural insight for the recognition of G-quadruplex structure at human c-myc promoter sequence by flavonoid Quercetin
title_fullStr	Structural insight for the recognition of G-quadruplex structure at human c-myc promoter sequence by flavonoid Quercetin
title_full_unstemmed	Structural insight for the recognition of G-quadruplex structure at human c-myc promoter sequence by flavonoid Quercetin
title_sort	structural insight for the recognition of g-quadruplex structure at human c-myc promoter sequence by flavonoid quercetin
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/d2ba3ee4825e4473966e93502f33a65e
work_keys_str_mv	AT arpitatawani structuralinsightfortherecognitionofgquadruplexstructureathumancmycpromotersequencebyflavonoidquercetin AT subodhkumarmishra structuralinsightfortherecognitionofgquadruplexstructureathumancmycpromotersequencebyflavonoidquercetin AT amitkumar structuralinsightfortherecognitionofgquadruplexstructureathumancmycpromotersequencebyflavonoidquercetin
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Structural insight for the recognition of G-quadruplex structure at human c-myc promoter sequence by flavonoid Quercetin

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