Chlorophyllin Inhibits Mammalian Thioredoxin Reductase 1 and Triggers Cancer Cell Death

Food colorants are widely used by humans in food production and preparation; however, their potential toxicity requires an in-depth analysis. In this study, five out of 15 commercial food colorants, namely, lutein, betanin, caramel, crocin and chlorophyll, significantly inhibited wild type selenopro...

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Autores principales:	Shibo Sun, Yici Zhang, Weiping Xu, Yue Zhang, Rui Yang, Jianli Guo, Shui Guan, Qiang Ma, Kun Ma, Jianqiang Xu
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	food colorants thioredoxin reductase chlorophyllin cell death selenocysteine SecTRAPs (selenium compromised thioredoxin reductase-derived apoptotic proteins) Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/c3b4f96c78ed4884a071755cd3eea1c3
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spelling	oai:doaj.org-article:c3b4f96c78ed4884a071755cd3eea1c32021-11-25T16:27:25ZChlorophyllin Inhibits Mammalian Thioredoxin Reductase 1 and Triggers Cancer Cell Death10.3390/antiox101117332076-3921https://doaj.org/article/c3b4f96c78ed4884a071755cd3eea1c32021-10-01T00:00:00Zhttps://www.mdpi.com/2076-3921/10/11/1733https://doaj.org/toc/2076-3921Food colorants are widely used by humans in food production and preparation; however, their potential toxicity requires an in-depth analysis. In this study, five out of 15 commercial food colorants, namely, lutein, betanin, caramel, crocin and chlorophyll, significantly inhibited wild type selenoprotein thioredoxin reductase 1 (TrxR1, TXNRD1) in vitro. The hyperactive Sec<sup>498</sup> residue of TrxR1 was targeted by those five colorants, which was confirmed by the site-directed mutagenesis of TrxR1. Furthermore, two colorants, chlorophyll and betanin, triggered the oligomerization of TrxR1. A chlorophyll-derived compound, chlorophyllin, irreversibly inhibited the 5,5′-dithiobis-2-nitrobenzoic acid (DTNB) reducing activity of TrxR1 with <i>K</i><sub>inact</sub> = 6.96 × 10<sup>−3</sup> ± 0.49 × 10<sup>−3</sup> µM<sup>−1</sup> min<sup>−1</sup>. Moreover, chlorophyllin reduced the cellular TrxR activity, leading to reactive oxygen species (ROS) accumulation and, subsequently, promoting cancer cell death. In conclusion, this study might contribute to understand the food safety of commercial colorants and provide chemotherapeutic compounds by targeting TrxR1.Shibo SunYici ZhangWeiping XuYue ZhangRui YangJianli GuoShui GuanQiang MaKun MaJianqiang XuMDPI AGarticlefood colorantsthioredoxin reductasechlorophyllincell deathselenocysteineSecTRAPs (selenium compromised thioredoxin reductase-derived apoptotic proteins)Therapeutics. PharmacologyRM1-950ENAntioxidants, Vol 10, Iss 1733, p 1733 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	food colorants thioredoxin reductase chlorophyllin cell death selenocysteine SecTRAPs (selenium compromised thioredoxin reductase-derived apoptotic proteins) Therapeutics. Pharmacology RM1-950
spellingShingle	food colorants thioredoxin reductase chlorophyllin cell death selenocysteine SecTRAPs (selenium compromised thioredoxin reductase-derived apoptotic proteins) Therapeutics. Pharmacology RM1-950 Shibo Sun Yici Zhang Weiping Xu Yue Zhang Rui Yang Jianli Guo Shui Guan Qiang Ma Kun Ma Jianqiang Xu Chlorophyllin Inhibits Mammalian Thioredoxin Reductase 1 and Triggers Cancer Cell Death
description	Food colorants are widely used by humans in food production and preparation; however, their potential toxicity requires an in-depth analysis. In this study, five out of 15 commercial food colorants, namely, lutein, betanin, caramel, crocin and chlorophyll, significantly inhibited wild type selenoprotein thioredoxin reductase 1 (TrxR1, TXNRD1) in vitro. The hyperactive Sec<sup>498</sup> residue of TrxR1 was targeted by those five colorants, which was confirmed by the site-directed mutagenesis of TrxR1. Furthermore, two colorants, chlorophyll and betanin, triggered the oligomerization of TrxR1. A chlorophyll-derived compound, chlorophyllin, irreversibly inhibited the 5,5′-dithiobis-2-nitrobenzoic acid (DTNB) reducing activity of TrxR1 with <i>K</i><sub>inact</sub> = 6.96 × 10<sup>−3</sup> ± 0.49 × 10<sup>−3</sup> µM<sup>−1</sup> min<sup>−1</sup>. Moreover, chlorophyllin reduced the cellular TrxR activity, leading to reactive oxygen species (ROS) accumulation and, subsequently, promoting cancer cell death. In conclusion, this study might contribute to understand the food safety of commercial colorants and provide chemotherapeutic compounds by targeting TrxR1.
format	article
author	Shibo Sun Yici Zhang Weiping Xu Yue Zhang Rui Yang Jianli Guo Shui Guan Qiang Ma Kun Ma Jianqiang Xu
author_facet	Shibo Sun Yici Zhang Weiping Xu Yue Zhang Rui Yang Jianli Guo Shui Guan Qiang Ma Kun Ma Jianqiang Xu
author_sort	Shibo Sun
title	Chlorophyllin Inhibits Mammalian Thioredoxin Reductase 1 and Triggers Cancer Cell Death
title_short	Chlorophyllin Inhibits Mammalian Thioredoxin Reductase 1 and Triggers Cancer Cell Death
title_full	Chlorophyllin Inhibits Mammalian Thioredoxin Reductase 1 and Triggers Cancer Cell Death
title_fullStr	Chlorophyllin Inhibits Mammalian Thioredoxin Reductase 1 and Triggers Cancer Cell Death
title_full_unstemmed	Chlorophyllin Inhibits Mammalian Thioredoxin Reductase 1 and Triggers Cancer Cell Death
title_sort	chlorophyllin inhibits mammalian thioredoxin reductase 1 and triggers cancer cell death
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/c3b4f96c78ed4884a071755cd3eea1c3
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Chlorophyllin Inhibits Mammalian Thioredoxin Reductase 1 and Triggers Cancer Cell Death

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