Chlorophyllin Inhibits Mammalian Thioredoxin Reductase 1 and Triggers Cancer Cell Death

Antioxidants

Qiang Ma¹  Yici Zhang²  Kun Ma³  Shibo Sun³  Jianli Guo³  Rui Yang³  Yue Zhang³  Jianqiang Xu³  Weiping Xu⁴  Shui Guan⁵ 

[1] Chinese Academy of Inspection and Quarantine, Beijing 100176, China;Interdisciplinary Research Center on Biology and Chemistry (IRCBC), Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 201210, China;School of Life and Pharmaceutical Sciences (LPS), Panjin Institute of Industrial Technology (PIIT), Liaoning Key Laboratory of Chemical Additive Synthesis and Separation (CASS), Dalian University of Technology, Panjin 124221, China;School of Ocean Science and Technology (OST), Dalian University of Technology, Panjin 124221, China;State Key Laboratory of Fine Chemicals, Dalian R & D Center for Stem Cell and Tissue Engineering, School of Chemical Engineering, Dalian University of Technology, Dalian 116023, China;

关键词: food colorants;    thioredoxin reductase;    chlorophyllin;    cell death;    selenocysteine;    SecTRAPs (selenium compromised thioredoxin reductase-derived apoptotic proteins);   

DOI  :  10.3390/antiox10111733

来源: DOAJ

【 摘 要 】

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 Sec⁴⁹⁸ 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 K_inact = 6.96 × 10⁻³ ± 0.49 × 10⁻³ µM⁻¹ min⁻¹. 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.

【 授权许可】

Unknown