Selenium speciation determines the angiogenesis effect through regulating selenoproteins to trigger ROS-mediated cell apoptosis and cell cycle arrest |
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| Affiliation: | 1. School of Pharmacy, Second Military Medical University, Shanghai 200433, China;2. Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (MOE), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Ji''nan 250012, China;1. Institute of Modern Optics and Center of Single-Molecule Science, Tianjin Key Laboratory of Micro-scale Optical Information Science and Technology, Nankai University, Tianjin 300350, China;2. School of Materials Science and Engineering, Smart Sensing Interdisciplinary Science Center, Nankai University, Tianjin 300350, China;1. Department of Chemistry, Jinan University, Guangzhou 510632, China;2. Department of Orthopedics, Affiliated Hospital of Guangdong Medical University, Zhanjiang 524001, China;1. Department of Ultrasound, Central Laboratory, Ningbo First Hospital, Ningbo 315000, China;2. Cixi Institute of Biomedical Engineering, International Cooperation Base of Biomedical Materials Technology and Application, Chinese Academy of Sciences (CAS) Key Laboratory of Magnetic Materials and Devices, Zhejiang Engineering Research Center for Biomedical Materials, Ningbo Institute of Materials Technology and Engineering, CAS, Ningbo 315201, China;3. University of Chinese Academy of Sciences, Beijing 100049, China |
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| Abstract: | Tumor angiogenesis is closely related to tumor development, immune escape, and drug resistance. Therefore, the development of effective anti-tumor angiogenesis drugs is of great research significance. Although the current clinical angiogenesis inhibitors have achieved certain efficacy, they also pose the problems of limited and short duration of efficacy, drug resistance, and intrinsic toxicity. Anti-tumor angiogenesis strategies targeting endothelial cells (ECs) have attracted widespread attention in the development of highly effective and low toxicity anti-angiogenesis inhibitors. Studies have verified that the trace element selenium (Se) can inhibit tumor growth by inhibiting tumor angiogenesis through different mechanisms. Nevertheless, it is unclear whether Se speciation has different effects on anti-tumor angiogenesis. Herein, we found that Se exhibited effective anti-angiogenic activity, and its mechanisms of activity were determined by its chemical speciation. Organic Se can significantly inhibit tumor angiogenesis by targeting thioredoxin reductase (TrxR) to trigger cell apoptosis and cell cycle arrest and by increasing reactive oxygen species (ROS) production in ECs. Inorganic Se can induce cell cycle arrest and increase ROS production in ECs, showing promising anti-angiogenic effects. Se nanoparticles (SeNPs) slightly inhibit tumor angiogenesis by inducing apoptosis and cell cycle arrest and by increasing the production of ROS. In summary, this study elucidates the anti-angiogenic activity of Se speciation control with a view to providing a scientific reference for the design and development of novel Se-based highly effective and low toxicity angiogenesis inhibitors. |
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