For Publishers
DiscoveryMetadataPeer reviewHostingPublishing
For Researchers
JoinPublishReviewCollect
Register
Blog
About
Search
Advanced search
My ScienceOpen
Search
For Publishers
For Researchers
Blog
About
14
views
38
references
 Top references
cited by
22
    
0 reviews
 Review
0
comments
 Comment
0
recommends
+1 Recommend
0 collections
    0
    shares
      529
      similar
       All similar
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Isobavachalcone Induces ROS-Mediated Apoptosis via Targeting Thioredoxin Reductase 1 in Human Prostate Cancer PC-3 Cells

      research-article

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Prostate carcinoma causes a great number of deaths every year; therefore, there is an urgent need to find new drug candidates to treat advanced prostate cancer. Isobavachalcone (IBC) is the chalcone composition of Psoralea corylifolia Linn used in traditional Chinese medicine. Although IBC demonstrates potent anticancer efficacy in numerous types of human cancer cells, the cellular targets of IBC have not been fully defined. In our study, we found that IBC may induce reactive oxygen species- (ROS-) mediated apoptosis via interaction with a selenocysteine (Sec) containing the antioxidant enzyme thioredoxin reductase 1 (TrxR1), and induce lethal endoplasmic reticulum (ER) stress by inhibiting TrxR1 activity and increasing ROS levels in human prostate cancer PC-3 cells. Furthermore, we also observed that knocking down TrxR1 would sensitized cancer cells to IBC treatment. Our study provides evidence for the anticancer mechanism of IBC with TrxR1 as a potential target.

          Related collections

          Most cited references38

          • Record: found
          • Abstract: found
          • Article: not found

          The thioredoxin antioxidant system.

          Jun Lu, Arne Holmgren (2014)
          The thioredoxin (Trx) system, which is composed of NADPH, thioredoxin reductase (TrxR), and thioredoxin, is a key antioxidant system in defense against oxidative stress through its disulfide reductase activity regulating protein dithiol/disulfide balance. The Trx system provides the electrons to thiol-dependent peroxidases (peroxiredoxins) to remove reactive oxygen and nitrogen species with a fast reaction rate. Trx antioxidant functions are also shown by involvement in DNA and protein repair by reducing ribonucleotide reductase, methionine sulfoxide reductases, and regulating the activity of many redox-sensitive transcription factors. Moreover, Trx systems play critical roles in the immune response, virus infection, and cell death via interaction with thioredoxin-interacting protein. In mammalian cells, the cytosolic and mitochondrial Trx systems, in which TrxRs are high molecular weight selenoenzymes, together with the glutathione-glutaredoxin (Grx) system (NADPH, glutathione reductase, GSH, and Grx) control the cellular redox environment. Recently mammalian thioredoxin and glutathione systems have been found to be able to provide the electrons crossly and to serve as a backup system for each other. In contrast, bacteria TrxRs are low molecular weight enzymes with a structure and reaction mechanism distinct from mammalian TrxR. Many bacterial species possess specific thiol-dependent antioxidant systems, and the significance of the Trx system in the defense against oxidative stress is different. Particularly, the absence of a GSH-Grx system in some pathogenic bacteria such as Helicobacter pylori, Mycobacterium tuberculosis, and Staphylococcus aureus makes the bacterial Trx system essential for survival under oxidative stress. This provides an opportunity to kill these bacteria by targeting the TrxR-Trx system. Copyright © 2013 Elsevier Inc. All rights reserved.
          Article 0 comments Cited 595 times – based on 0 reviews     Review now
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            The endoplasmic reticulum and the unfolded protein response.

            Jyoti Malhotra, Randal Kaufman (2007)
            The endoplasmic reticulum (ER) is the site where proteins enter the secretory pathway. Proteins are translocated into the ER lumen in an unfolded state and require protein chaperones and catalysts of protein folding to attain their final appropriate conformation. A sensitive surveillance mechanism exists to prevent misfolded proteins from transiting the secretory pathway and ensures that persistently misfolded proteins are directed towards a degradative pathway. In addition, those processes that prevent accumulation of unfolded proteins in the ER lumen are highly regulated by an intracellular signaling pathway known as the unfolded protein response (UPR). The UPR provides a mechanism by which cells can rapidly adapt to alterations in client protein-folding load in the ER lumen by expanding the capacity for protein folding. In addition, a variety of insults that disrupt protein folding in the ER lumen also activate the UPR. These include changes in intralumenal calcium, altered glycosylation, nutrient deprivation, pathogen infection, expression of folding-defective proteins, and changes in redox status. Persistent protein misfolding initiates apoptotic cascades that are now known to play fundamental roles in the pathogenesis of multiple human diseases including diabetes, atherosclerosis and neurodegenerative diseases.
            Article 0 comments Cited 288 times – based on 0 reviews     Review now
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Focus on mammalian thioredoxin reductases--important selenoproteins with versatile functions.

              E S J Arnér (2009)
              Thioredoxin systems, involving redox active thioredoxins and thioredoxin reductases, sustain a number of important thioredoxin-dependent pathways. These redox active proteins support several processes crucial for cell function, cell proliferation, antioxidant defense and redox-regulated signaling cascades. Mammalian thioredoxin reductases are selenium-containing flavoprotein oxidoreductases, dependent upon a selenocysteine residue for reduction of the active site disulfide in thioredoxins. Their activity is required for normal thioredoxin function. The mammalian thioredoxin reductases also display surprisingly multifaceted properties and functions beyond thioredoxin reduction. Expressed from three separate genes (in human named TXNRD1, TXNRD2 and TXNRD3), the thioredoxin reductases can each reduce a number of different types of substrates in different cellular compartments. Their expression patterns involve intriguingly complex transcriptional mechanisms resulting in several splice variants, encoding a number of protein variants likely to have specialized functions in a cell- and tissue-type restricted manner. The thioredoxin reductases are also targeted by a number of drugs and compounds having an impact on cell function and promoting oxidative stress, some of which are used in treatment of rheumatoid arthritis, cancer or other diseases. However, potential specific or essential roles for different forms of human or mouse thioredoxin reductases in health or disease are still rather unclear, although it is known that at least the murine Txnrd1 and Txnrd2 genes are essential for normal development during embryogenesis. This review is a survey of current knowledge of mammalian thioredoxin reductase function and expression, with a focus on human and mouse and a discussion of the striking complexity of these proteins. Several yet open questions regarding their regulation and roles in different cells or tissues are emphasized. It is concluded that the intriguingly complex regulation and function of mammalian thioredoxin reductases within the cellular context and in intact mammals strongly suggests that their functions are highly fi ne-tuned with the many pathways involving thioredoxins and thioredoxin-related proteins. These selenoproteins furthermore propagate many functions beyond a reduction of thioredoxins. Aberrant regulation of thioredoxin reductases, or a particular dependence upon these enzymes in diseased cells, may underlie their presumed therapeutic importance as enzymatic targets using electrophilic drugs. These reductases are also likely to mediate several of the effects on health and disease that are linked to different levels of nutritional selenium intake. The thioredoxin reductases and their splice variants may be pivotal components of diverse cellular signaling pathways, having importance in several redox-related aspects of health and disease. Clearly, a detailed understanding of mammalian thioredoxin reductases is necessary for a full comprehension of the thioredoxin system and of selenium dependent processes in mammals.
              Article 0 comments Cited 168 times – based on 0 reviews     Review now
                Bookmark
                All references

                Author and article information

                Contributors
                Jianning Wang:
                ORCID: http://orcid.org/0000-0003-4450-8925
                Journal
                Journal ID (nlm-ta): Oxid Med Cell Longev
                Journal ID (iso-abbrev): Oxid Med Cell Longev
                Journal ID (publisher-id): OMCL
                Title: Oxidative Medicine and Cellular Longevity
                Publisher: Hindawi
                ISSN (Print): 1942-0900
                ISSN (Electronic): 1942-0994
                Publication date Collection: 2018
                Publication date (Electronic): 16 October 2018
                Volume: 2018
                Electronic Location Identifier: 1915828
                Affiliations
                1Department of Urology, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan 250014, China
                2Binzhou Medical University, Yantai, Shandong 264003, China
                Author notes

                Academic Editor: Kum Kum Khanna

                Author information
                http://orcid.org/0000-0001-6413-9878
                http://orcid.org/0000-0003-4450-8925
                Article
                DOI: 10.1155/2018/1915828
                PMC ID: 6206523
                PubMed ID: 30410640
                SO-VID: c037792c-8279-4d9c-bc1a-c1c12f24da82
                Copyright © Copyright © 2018 Kai Li et al.
                License:

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Date received : 15 January 2018
                Date revision received : 2 July 2018
                Date accepted : 1 August 2018
                Funding
                Funded by: Shangdong Province
                Award ID: 2016GSF121027
                Categories
                Subject: Research Article

                ScienceOpen disciplines: Molecular medicine
                Data availability:
                ScienceOpen disciplines: Molecular medicine

                Comments

                Comment on this article

                scite_

                Similar content529

                See all similar

                Cited by21

                See all cited by

                Most referenced authors807

                See all reference authors