Potential chemopreventive, anticancer and anti-inflammatory properties of a refined artocarpin-rich wood extract of Artocarpus heterophyllus Lam.

Abstract Colorectal cancer (CRC) represents the third leading cause of death among cancer patients below the age of 50, necessitating improved treatment and prevention initiatives. A crude methanol extract from the wood pulp of Artocarpus heterophyllus was found to be the most bioactive among multip...

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Autores principales:	Isaac J. Morrison, Jianan Zhang, Jingwen Lin, JeAnn E. Murray, Roy Porter, Moses K. Langat, Nicholas J. Sadgrove, James Barker, Guodong Zhang, Rupika Delgoda
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/9b0ad63342ff425e961a3df102f7d8ad
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spelling	oai:doaj.org-article:9b0ad63342ff425e961a3df102f7d8ad2021-12-02T13:24:26ZPotential chemopreventive, anticancer and anti-inflammatory properties of a refined artocarpin-rich wood extract of Artocarpus heterophyllus Lam.10.1038/s41598-021-86040-52045-2322https://doaj.org/article/9b0ad63342ff425e961a3df102f7d8ad2021-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-86040-5https://doaj.org/toc/2045-2322Abstract Colorectal cancer (CRC) represents the third leading cause of death among cancer patients below the age of 50, necessitating improved treatment and prevention initiatives. A crude methanol extract from the wood pulp of Artocarpus heterophyllus was found to be the most bioactive among multiple others, and an enriched extract containing 84% (w/v) artocarpin (determined by HPLC–MS–DAD) was prepared. The enriched extract irreversibly inhibited the activity of human cytochrome P450 CYP2C9, an enzyme previously shown to be overexpressed in CRC models. In vitro evaluations on heterologously expressed microsomes, revealed irreversible inhibitory kinetics with an IC50 value of 0.46 µg/mL. Time- and concentration-dependent cytotoxicity was observed on human cancerous HCT116 cells with an IC50 value of 4.23 mg/L in 72 h. We then employed the azoxymethane (AOM)/dextran sodium sulfate (DSS) colitis-induced model in C57BL/6 mice, which revealed that the enriched extract suppressed tumor multiplicity, reduced the protein expression of proliferating cell nuclear antigen, and attenuated the gene expression of proinflammatory cytokines (Il-6 and Ifn-γ) and protumorigenic markers (Pcna, Axin2, Vegf, and Myc). The extract significantly (p = 0.03) attenuated (threefold) the gene expression of murine Cyp2c37, an enzyme homologous to the human CYP2C9 enzyme. These promising chemopreventive, cytotoxic, anticancer and anti-inflammatory responses, combined with an absence of toxicity, validate further evaluation of A. heterophyllus extract as a therapeutic agent.Isaac J. MorrisonJianan ZhangJingwen LinJeAnn E. MurrayRoy PorterMoses K. LangatNicholas J. SadgroveJames BarkerGuodong ZhangRupika DelgodaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Isaac J. Morrison Jianan Zhang Jingwen Lin JeAnn E. Murray Roy Porter Moses K. Langat Nicholas J. Sadgrove James Barker Guodong Zhang Rupika Delgoda Potential chemopreventive, anticancer and anti-inflammatory properties of a refined artocarpin-rich wood extract of Artocarpus heterophyllus Lam.
description	Abstract Colorectal cancer (CRC) represents the third leading cause of death among cancer patients below the age of 50, necessitating improved treatment and prevention initiatives. A crude methanol extract from the wood pulp of Artocarpus heterophyllus was found to be the most bioactive among multiple others, and an enriched extract containing 84% (w/v) artocarpin (determined by HPLC–MS–DAD) was prepared. The enriched extract irreversibly inhibited the activity of human cytochrome P450 CYP2C9, an enzyme previously shown to be overexpressed in CRC models. In vitro evaluations on heterologously expressed microsomes, revealed irreversible inhibitory kinetics with an IC50 value of 0.46 µg/mL. Time- and concentration-dependent cytotoxicity was observed on human cancerous HCT116 cells with an IC50 value of 4.23 mg/L in 72 h. We then employed the azoxymethane (AOM)/dextran sodium sulfate (DSS) colitis-induced model in C57BL/6 mice, which revealed that the enriched extract suppressed tumor multiplicity, reduced the protein expression of proliferating cell nuclear antigen, and attenuated the gene expression of proinflammatory cytokines (Il-6 and Ifn-γ) and protumorigenic markers (Pcna, Axin2, Vegf, and Myc). The extract significantly (p = 0.03) attenuated (threefold) the gene expression of murine Cyp2c37, an enzyme homologous to the human CYP2C9 enzyme. These promising chemopreventive, cytotoxic, anticancer and anti-inflammatory responses, combined with an absence of toxicity, validate further evaluation of A. heterophyllus extract as a therapeutic agent.
format	article
author	Isaac J. Morrison Jianan Zhang Jingwen Lin JeAnn E. Murray Roy Porter Moses K. Langat Nicholas J. Sadgrove James Barker Guodong Zhang Rupika Delgoda
author_facet	Isaac J. Morrison Jianan Zhang Jingwen Lin JeAnn E. Murray Roy Porter Moses K. Langat Nicholas J. Sadgrove James Barker Guodong Zhang Rupika Delgoda
author_sort	Isaac J. Morrison
title	Potential chemopreventive, anticancer and anti-inflammatory properties of a refined artocarpin-rich wood extract of Artocarpus heterophyllus Lam.
title_short	Potential chemopreventive, anticancer and anti-inflammatory properties of a refined artocarpin-rich wood extract of Artocarpus heterophyllus Lam.
title_full	Potential chemopreventive, anticancer and anti-inflammatory properties of a refined artocarpin-rich wood extract of Artocarpus heterophyllus Lam.
title_fullStr	Potential chemopreventive, anticancer and anti-inflammatory properties of a refined artocarpin-rich wood extract of Artocarpus heterophyllus Lam.
title_full_unstemmed	Potential chemopreventive, anticancer and anti-inflammatory properties of a refined artocarpin-rich wood extract of Artocarpus heterophyllus Lam.
title_sort	potential chemopreventive, anticancer and anti-inflammatory properties of a refined artocarpin-rich wood extract of artocarpus heterophyllus lam.
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/9b0ad63342ff425e961a3df102f7d8ad
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Potential chemopreventive, anticancer and anti-inflammatory properties of a refined artocarpin-rich wood extract of Artocarpus heterophyllus Lam.

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