Cytochrome P450 isoforms 1A1, 1B1 AND 2W1 as targets for therapeutic intervention in head and neck cancer

Abstract Epidemiological studies have shown that head and neck cancer (HNC) is a complex multistage process that in part involves exposure to a combination of carcinogens and the capacity of certain drug-metabolising enzymes including cytochrome P450 (CYP) to detoxify or activate such carcinogens. I...

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Autores principales:	Daniela Presa, Syed A. Khurram, Amir Z. A. Zubir, Sneha Smarakan, Patricia A. Cooper, Goreti R. Morais, Maria Sadiq, Mark Sutherland, Paul M. Loadman, James McCaul, Steven D. Shnyder, Laurence H. Patterson, Klaus Pors
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/4ea9b86b01fd4ec18d301c0d665c1e69
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spelling	oai:doaj.org-article:4ea9b86b01fd4ec18d301c0d665c1e692021-12-02T15:14:47ZCytochrome P450 isoforms 1A1, 1B1 AND 2W1 as targets for therapeutic intervention in head and neck cancer10.1038/s41598-021-98217-z2045-2322https://doaj.org/article/4ea9b86b01fd4ec18d301c0d665c1e692021-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-98217-zhttps://doaj.org/toc/2045-2322Abstract Epidemiological studies have shown that head and neck cancer (HNC) is a complex multistage process that in part involves exposure to a combination of carcinogens and the capacity of certain drug-metabolising enzymes including cytochrome P450 (CYP) to detoxify or activate such carcinogens. In this study, CYP1A1, CYP1B1 and CYP2W1 expression in HNC was correlated with potential as target for duocarmycin prodrug activation and selective therapy. In the HNC cell lines, elevated expression was shown at the gene level for CYP1A1 and CYP1B1 whereas CYP2W1 was hardly detected. However, CYP2W1 was expressed in FaDu and Detroit-562 xenografts and in a cohort of human HNC samples. Functional activity was measured in Fadu and Detroit-562 cells using P450-Glo™ assay. Antiproliferative results of duocarmycin prodrugs ICT2700 and ICT2706 revealed FaDu and Detroit-562 as the most sensitive HNC cell lines. Administration of ICT2700 in vivo using a single dose of ICT2700 (150 mg/kg) showed preferential inhibition of small tumour growth (mean size of 60 mm3) in mice bearing FaDu xenografts. Significantly, our findings suggest a potential targeted therapeutic approach to manage HNCs by exploiting intratumoural CYP expression for metabolic activation of duocarmycin-based prodrugs such as ICT2700.Daniela PresaSyed A. KhurramAmir Z. A. ZubirSneha SmarakanPatricia A. CooperGoreti R. MoraisMaria SadiqMark SutherlandPaul M. LoadmanJames McCaulSteven D. ShnyderLaurence H. PattersonKlaus PorsNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Daniela Presa Syed A. Khurram Amir Z. A. Zubir Sneha Smarakan Patricia A. Cooper Goreti R. Morais Maria Sadiq Mark Sutherland Paul M. Loadman James McCaul Steven D. Shnyder Laurence H. Patterson Klaus Pors Cytochrome P450 isoforms 1A1, 1B1 AND 2W1 as targets for therapeutic intervention in head and neck cancer
description	Abstract Epidemiological studies have shown that head and neck cancer (HNC) is a complex multistage process that in part involves exposure to a combination of carcinogens and the capacity of certain drug-metabolising enzymes including cytochrome P450 (CYP) to detoxify or activate such carcinogens. In this study, CYP1A1, CYP1B1 and CYP2W1 expression in HNC was correlated with potential as target for duocarmycin prodrug activation and selective therapy. In the HNC cell lines, elevated expression was shown at the gene level for CYP1A1 and CYP1B1 whereas CYP2W1 was hardly detected. However, CYP2W1 was expressed in FaDu and Detroit-562 xenografts and in a cohort of human HNC samples. Functional activity was measured in Fadu and Detroit-562 cells using P450-Glo™ assay. Antiproliferative results of duocarmycin prodrugs ICT2700 and ICT2706 revealed FaDu and Detroit-562 as the most sensitive HNC cell lines. Administration of ICT2700 in vivo using a single dose of ICT2700 (150 mg/kg) showed preferential inhibition of small tumour growth (mean size of 60 mm3) in mice bearing FaDu xenografts. Significantly, our findings suggest a potential targeted therapeutic approach to manage HNCs by exploiting intratumoural CYP expression for metabolic activation of duocarmycin-based prodrugs such as ICT2700.
format	article
author	Daniela Presa Syed A. Khurram Amir Z. A. Zubir Sneha Smarakan Patricia A. Cooper Goreti R. Morais Maria Sadiq Mark Sutherland Paul M. Loadman James McCaul Steven D. Shnyder Laurence H. Patterson Klaus Pors
author_facet	Daniela Presa Syed A. Khurram Amir Z. A. Zubir Sneha Smarakan Patricia A. Cooper Goreti R. Morais Maria Sadiq Mark Sutherland Paul M. Loadman James McCaul Steven D. Shnyder Laurence H. Patterson Klaus Pors
author_sort	Daniela Presa
title	Cytochrome P450 isoforms 1A1, 1B1 AND 2W1 as targets for therapeutic intervention in head and neck cancer
title_short	Cytochrome P450 isoforms 1A1, 1B1 AND 2W1 as targets for therapeutic intervention in head and neck cancer
title_full	Cytochrome P450 isoforms 1A1, 1B1 AND 2W1 as targets for therapeutic intervention in head and neck cancer
title_fullStr	Cytochrome P450 isoforms 1A1, 1B1 AND 2W1 as targets for therapeutic intervention in head and neck cancer
title_full_unstemmed	Cytochrome P450 isoforms 1A1, 1B1 AND 2W1 as targets for therapeutic intervention in head and neck cancer
title_sort	cytochrome p450 isoforms 1a1, 1b1 and 2w1 as targets for therapeutic intervention in head and neck cancer
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/4ea9b86b01fd4ec18d301c0d665c1e69
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Cytochrome P450 isoforms 1A1, 1B1 AND 2W1 as targets for therapeutic intervention in head and neck cancer

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