Chlorophyllin Inhibits Mammalian Thioredoxin Reductase 1 and Triggers Cancer Cell Death
Shibo Sun,
Yici Zhang,
Weiping Xu,
Yue Zhang,
Rui Yang,
Jianli Guo,
Shui Guan,
Qiang Ma,
Kun Ma,
Jianqiang Xu
Affiliations
Shibo Sun
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
Yici Zhang
Interdisciplinary Research Center on Biology and Chemistry (IRCBC), Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 201210, China
Weiping Xu
School of Ocean Science and Technology (OST), Dalian University of Technology, Panjin 124221, China
Yue Zhang
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
Rui Yang
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
Jianli Guo
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
Shui Guan
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
Qiang Ma
Chinese Academy of Inspection and Quarantine, Beijing 100176, China
Kun Ma
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
Jianqiang Xu
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
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 Kinact = 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.
