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Peroxiredoxin 3 Is A Redox-Dependent Target Of Thiostrepton In Malignant Mesothelioma Cells

Kheng Newick, B. Cunniff, Kelsey Preston, P. Held, J. Arbiser, H. Pass, B. Mossman, A. Shukla, N. Heintz
Published 2012 · Biology, Medicine

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Thiostrepton (TS) is a thiazole antibiotic that inhibits expression of FOXM1, an oncogenic transcription factor required for cell cycle progression and resistance to oncogene-induced oxidative stress. The mechanism of action of TS is unclear and strategies that enhance TS activity will improve its therapeutic potential. Analysis of human tumor specimens showed FOXM1 is broadly expressed in malignant mesothelioma (MM), an intractable tumor associated with asbestos exposure. The mechanism of action of TS was investigated in a cell culture model of human MM. As for other tumor cell types, TS inhibited expression of FOXM1 in MM cells in a dose-dependent manner. Suppression of FOXM1 expression and coincidental activation of ERK1/2 by TS were abrogated by pre-incubation of cells with the antioxidant N-acetyl-L-cysteine (NAC), indicating its mechanism of action in MM cells is redox-dependent. Examination of the mitochondrial thioredoxin reductase 2 (TR2)-thioredoxin 2 (TRX2)-peroxiredoxin 3 (PRX3) antioxidant network revealed that TS modifies the electrophoretic mobility of PRX3. Incubation of recombinant human PRX3 with TS in vitro also resulted in PRX3 with altered electrophoretic mobility. The cellular and recombinant species of modified PRX3 were resistant to dithiothreitol and SDS and suppressed by NAC, indicating that TS covalently adducts cysteine residues in PRX3. Reduction of endogenous mitochondrial TRX2 levels by the cationic triphenylmethane gentian violet (GV) promoted modification of PRX3 by TS and significantly enhanced its cytotoxic activity. Our results indicate TS covalently adducts PRX3, thereby disabling a major mitochondrial antioxidant network that counters chronic mitochondrial oxidative stress. Redox-active compounds like GV that modify the TR2/TRX2 network may significantly enhance the efficacy of TS, thereby providing a combinatorial approach for exploiting redox-dependent perturbations in mitochondrial function as a therapeutic approach in mesothelioma.
This paper references
10.6004/JNCCN.2012.0006
[Malignant pleural mesothelioma].
Q. Kong (1983)
Characterization of a human malignant mesothelioma cell line (H-MESO-1): a biphasic solid and ascitic tumor model.
Frank R. Reale (1987)
10.1590/S0074-02761988000500015
The metabolism and mode of action of gentian violet.
R. Docampo (1988)
10.1007/978-3-642-10862-4
[Malignant mesothelioma].
J. Espinosa Arranz (1994)
10.1016/0003-4975(95)00045-M
Characteristics of nine newly derived mesothelioma cell lines.
H. Pass (1995)
10.1021/BI952073E
Characterization of the covalent binding of thiostrepton to a thiostrepton-induced protein from Streptomyces lividans.
M. Chiu (1996)
10.1006/GENO.1997.5065
The human TRIDENT/HFH-11/FKHL16 gene: structure, localization, and promoter characterization.
W. Korver (1997)
10.1093/NAR/25.9.1715
The winged-helix transcription factor Trident is expressed in cycling cells.
W. Korver (1997)
10.1046/J.1432-0436.2000.660404.X
Upregulation of 9 genes, including that for thioredoxin, during epithelial differentiation of mesothelioma cells.
X. Sun (2000)
10.1016/S0891-5849(01)00724-9
Reactive oxygen species, antioxidants, and the mammalian thioredoxin system.
J. Nordberg (2001)
10.1002/1097-0215(20010520)95:3<198::AID-IJC1034>3.0.CO;2-F
Up‐regulation of thioredoxin and thioredoxin reductase in human malignant pleural mesothelioma
K. Kahlos (2001)
10.1002/path.1042
Overexpression of peroxiredoxins I, II, III, V, and VI in malignant mesothelioma
V. Kinnula (2002)
10.1152/AJPLUNG.00038.2003
Asbestos induces mitochondrial DNA damage and dysfunction linked to the development of apoptosis.
A. Shukla (2003)
10.1158/0008-5472.CAN-04-0946
The Duration of Nuclear Extracellular Signal-Regulated Kinase 1 and 2 Signaling during Cell Cycle Reentry Distinguishes Proliferation from Apoptosis in Response to Asbestos
Z. Yuan (2004)
10.1128/MCB.24.7.2649-2661.2004
Forkhead Box M1B Transcriptional Activity Requires Binding of Cdk-Cyclin Complexes for Phosphorylation-Dependent Recruitment of p300/CBP Coactivators
M. Major (2004)
10.1128/MCB.24.11.4696-4709.2004
An Extracellular Signal-Regulated Kinase 1- and 2-Dependent Program of Chromatin Trafficking of c-Fos and Fra-1 Is Required for Cyclin D1 Expression during Cell Cycle Reentry
P. Burch (2004)
10.1074/jbc.M312846200
Investigating Mitochondrial Redox Potential with Redox-sensitive Green Fluorescent Protein Indicators*
George T. Hanson (2004)
10.1242/jcs.01657
Raf/MEK/MAPK signaling stimulates the nuclear translocation and transactivating activity of FOXM1c
R. Y. M. Ma (2005)
10.1074/jbc.M504182200
Interactions of the N-terminal Domain of Ribosomal Protein L11 with Thiostrepton and rRNA*
Sarae L Bausch (2005)
10.1038/SJ.JID.5700413
Pharmacologic blockade of angiopoietin-2 is efficacious against model hemangiomas in mice.
B. Perry (2006)
10.1083/jcb.200606005
Oxidation state governs structural transitions in peroxiredoxin II that correlate with cell cycle arrest and recovery
T. Phalen (2006)
10.1158/0008-5472.CAN-06-1576
Identification of a chemical inhibitor of the oncogenic transcription factor forkhead box M1.
S. Radhakrishnan (2006)
10.1093/CARCIN/BGI222
Glutathione depletion by buthionine sulfoximine induces DNA deletions in mice.
R. Reliene (2006)
10.1016/J.BBCAN.2006.08.006
FoxM1: at the crossroads of ageing and cancer.
J. Laoukili (2007)
10.1042/BJ20061903
NOX4 activity is determined by mRNA levels and reveals a unique pattern of ROS generation.
L. Serrander (2007)
10.1038/nrc2223
The emerging roles of forkhead box (Fox) proteins in cancer
S. S. Myatt (2007)
10.1172/JCI27527
A cell-penetrating ARF peptide inhibitor of FoxM1 in mouse hepatocellular carcinoma treatment.
G. Gusarova (2007)
10.1021/bi800498g
Development of a family of redox-sensitive green fluorescent protein indicators for use in relatively oxidizing subcellular environments.
J. Lohman (2008)
10.1038/onc.2008.23
Many forks in the path: cycling with FoxO
K. K. Ho (2008)
10.1158/1535-7163.MCT-08-0188
Thiostrepton selectively targets breast cancer cells through inhibition of forkhead box M1 expression
J. Kwok (2008)
10.1016/j.freeradbiomed.2008.04.030
Mitochondrial peroxiredoxin 3 is rapidly oxidized in cells treated with isothiocyanates.
Kristin K. Brown (2008)
10.1128/MCB.00387-08
Anaphase-Promoting Complex/Cyclosome-Cdh1-Mediated Proteolysis of the Forkhead Box M1 Transcription Factor Is Critical for Regulated Entry into S Phase
H. Park (2008)
10.4161/cc.7.17.6580
FoxM1 is degraded at mitotic exit in a Cdh1-dependent manner
J. Laoukili (2008)
10.1111/j.1748-1716.2007.01780.x
FOXO transcription factors in ageing and cancer
E. L. Greer (2007)
10.1016/j.freeradbiomed.2008.03.011
Redox-based regulation of signal transduction: principles, pitfalls, and promises.
Y. Janssen-Heininger (2008)
10.1128/MCB.01710-07
Activation of FoxM1 during G2 Requires Cyclin A/Cdk-Dependent Relief of Autorepression by the FoxM1 N-Terminal Domain
J. Laoukili (2008)
10.1038/onc.2008.29
A brief introduction to FOXOlogy
B. M. Burgering (2008)
10.1111/j.1755-148X.2008.00451.x
The reactive oxygen‐driven tumor: relevance to melanoma
L. Fried (2008)
10.1136/gut.2008.152652
Forkhead box M1B is a determinant of rat susceptibility to hepatocarcinogenesis and sustains ERK activity in human HCC
D. Calvisi (2009)
10.1016/j.freeradbiomed.2009.05.026
The cell cycle is a redox cycle: linking phase-specific targets to cell fate.
W. Burhans (2009)
10.1002/anie.200804851
Hydrocyanines: a class of fluorescent sensors that can image reactive oxygen species in cell culture, tissue, and in vivo.
Kousik Kundu (2009)
10.1158/1535-7163.MCT-08-0805
Gefitinib (Iressa) represses FOXM1 expression via FOXO3a in breast cancer
U. McGovern (2009)
10.1038/nrd2803
Targeting cancer cells by ROS-mediated mechanisms: a radical therapeutic approach?
D. Trachootham (2009)
10.1089/ARS.2009.2541
Redox-directed cancer therapeutics: molecular mechanisms and opportunities.
G. Wondrak (2009)
10.1371/journal.pone.0005592
Thiazole Antibiotics Target FoxM1 and Induce Apoptosis in Human Cancer Cells
U. Bhat (2009)
10.1371/journal.pone.0006593
FoxM1 Is a General Target for Proteasome Inhibitors
U. Bhat (2009)
10.1200/JCO.2008.19.8523
Malignant pleural mesothelioma.
A. Tsao (2009)
10.3892/OR_00000366
Expression of human peroxiredoxin isoforms in response to cervical carcinogenesis.
Kiyoon Kim (2009)
10.1371/journal.pone.0004849
FOXM1 Upregulation Is an Early Event in Human Squamous Cell Carcinoma and it Is Enhanced by Nicotine during Malignant Transformation
E. Gemenetzidis (2009)
10.3892/IJO_00000313
FoxM1 is a downstream target and marker of HER2 overexpression in breast cancer.
R. E. Francis (2009)
10.1042/BJ20091541
Mitochondrial peroxiredoxin involvement in antioxidant defence and redox signalling.
A. G. Cox (2010)
10.1021/bi900558g
Redox potential and peroxide reactivity of human peroxiredoxin 3.
Andrew G. Cox (2009)
10.1042/BJ20090242
Mitochondrial peroxiredoxin 3 is more resilient to hyperoxidation than cytoplasmic peroxiredoxins.
Andrew G. Cox (2009)
10.1038/emboj.2009.239
FoxM1, a critical regulator of oxidative stress during oncogenesis
H. Park (2009)
10.1016/j.freeradbiomed.2010.01.028
Hydroethidine- and MitoSOX-derived red fluorescence is not a reliable indicator of intracellular superoxide formation: another inconvenient truth.
J. Zielonka (2010)
10.3892/IJO_00000507
Silencing the Peroxiredoxin III gene inhibits cell proliferation in breast cancer.
Pei-Jou Chua (2010)
10.4161/cc.9.6.10955
Thiazole antibiotics against breast cancer
M. Halasi (2010)
10.1016/j.tibs.2010.04.002
Mitochondrial reactive oxygen species regulate cellular signaling and dictate biological outcomes.
Robert B Hamanaka (2010)
10.1158/1541-7786.MCR-09-0432
FOXM1 Confers Acquired Cisplatin Resistance in Breast Cancer Cells
J. Kwok (2010)
10.1016/j.taap.2009.11.028
Oxidative stress and oxidative damage in chemical carcinogenesis.
J. Klaunig (2011)
10.4161/cc.10.19.17735
FoxM1 knockdown sensitizes human cancer cells to proteasome inhibitor-induced apoptosis but not to autophagy
Bulbul Pandit (2011)
10.1158/1535-7163.MCT-11-0024
ATM and p53 Regulate FOXM1 Expression via E2F in Breast Cancer Epirubicin Treatment and Resistance
J. Millour (2011)
10.1371/journal.pone.0017110
Thiazole Antibiotic Thiostrepton Synergize with Bortezomib to Induce Apoptosis in Cancer Cells
Bulbul Pandit (2011)
10.1002/pros.21292
Differential expression of peroxiredoxins in prostate cancer: Consistent upregulation of PRDX3 and PRDX4
Anamika Basu (2011)
10.1016/j.freeradbiomed.2010.12.036
Disruption of the mitochondrial thioredoxin system as a cell death mechanism of cationic triphenylmethanes.
X. Zhang (2011)
10.1038/nchem.1114
The transcription factor FOXM1 is a cellular target of the natural product thiostrepton.
Nagaratna S. Hegde (2011)
10.1038/NRC3108
Otto Warburg's contributions to current concepts of cancer metabolism
W. Koppenol (2011)
Differential expression of peroxiredoxins in
A Basu (2011)
10.1111/j.1755-148X.2012.00986.x
Systematic classification of melanoma cells by phenotype‐specific gene expression mapping
D. Widmer (2012)
10.1016/j.bcp.2012.01.027
Thiostrepton is an inducer of oxidative and proteotoxic stress that impairs viability of human melanoma cells but not primary melanocytes.
Shuxi Qiao (2012)
10.1002/jcp.22788
Targeting mitochondria as a therapeutic target in cancer
C. Wenner (2012)
10.1016/j.bbagrm.2011.09.004
FOXM1: From cancer initiation to progression and treatment.
Chuay-Yeng Koo (2012)
10.1097/CCO.0b013e32834d813b
SIRT1, metabolism and cancer
John R P Knight (2012)
10.3892/ijmm.2012.916
Detection and identification of peroxiredoxin 3 as a biomarker in hepatocellular carcinoma by a proteomic approach.
B. Qiao (2012)
cancer : consistent upregulation of PRDX 3 and PRDX 4
B Qiao (2012)



This paper is referenced by
10.1016/J.ARRES.2021.100008
Maneb adducts human peroxiredoxin 3 through thiol interactions
C. Anderson (2021)
10.1089/ars.2019.7752
Peroxiredoxins and Beyond; Redox Systems Regulating Lung Physiology and Disease.
E. Elko (2019)
10.3390/antiox8010011
Peroxiredoxins in Cancer and Response to Radiation Therapies
T. Forshaw (2019)
10.1038/s41598-019-43399-w
Identification of thiostrepton as a pharmacological approach to rescue misfolded alpha-sarcoglycan mutant proteins from degradation
L. Hoch (2019)
10.15430/JCP.2019.24.2.65
The Role of Peroxiredoxin Family in Cancer Signaling
Yosup Kim (2019)
10.3390/antiox7100136
Peroxiredoxins in Colorectal Cancer: Predictive Biomarkers of Radiation Response and Therapeutic Targets to Increase Radiation Sensitivity?
J. Fischer (2018)
10.1089/ars.2017.7422
Peroxiredoxin Involvement in the Initiation and Progression of Human Cancer.
M. Hampton (2017)
10.25148/etd.FIDC006857
Interaction of High Molecular Weight Compounds with a, β-Unsaturated Carbonyl Moiety with Mammalian and Drosophila Melanogaster Thioredoxin Reductase
Anupama Tuladhar (2018)
10.1016/j.bbagen.2016.10.023
Cellular ROS imaging with hydro-Cy3 dye is strongly influenced by mitochondrial membrane potential.
A. Zhdanov (2017)
10.1038/s41598-017-15108-y
Identification of claudin-4 binder that attenuates tight junction barrier function by TR-FRET-based screening assay
A. Watari (2017)
10.1039/C7ME00014F
Hydrocyanines: a versatile family of probes for imaging radical oxidants in vitro and in vivo
Corinne M Sadlowski (2017)
Effect of Hardaliye on FoxM 1 Gene Expression Level of HT-29 , DU-145 , HeLa Cancer Cells and CF-1 ( Mouse Embryonic Fibroblast )
Akademik Gıda (2017)
10.1007/978-3-319-53560-9_10
Cell Signaling and Epigenetic Mechanisms in Mesothelioma
B. Mossman (2017)
10.1021/acschembio.5b00731
Thiostrepton Variants Containing a Contracted Quinaldic Acid Macrocycle Result from Mutagenesis of the Second Residue.
F. Zhang (2016)
10.1016/B978-0-12-803269-5.00008-5
Chapter Eight – Hydrocyanines: A Versatile Family of Probes for Imaging Radical Oxidants In Vitro and In Vivo
K. Kundu (2016)
10.1016/B978-0-12-802508-6.00021-1
Copy Number Networks to Guide Combinatorial Therapy of Cancer and Proliferative Disorders
A. Lin (2015)
10.1111/jcmm.12602
Thiostrepton interacts covalently with Rpt subunits of the 19S proteasome and proteasome substrates
C. Sandu (2015)
10.1016/j.freeradbiomed.2015.05.002
Malignant mesothelioma as an oxidative stress-induced cancer: An update.
S. H. Chew (2015)
10.1016/j.freeradbiomed.2015.03.022
The cysteine proteome.
Y. Go (2015)
10.1371/journal.pone.0145404
Inflammasome Modulation by Chemotherapeutics in Malignant Mesothelioma
Catherine M. Westbom (2015)
10.1155/2015/267027
Metallothionein-I/II Knockout Mice Aggravate Mitochondrial Superoxide Production and Peroxiredoxin 3 Expression in Thyroid after Excessive Iodide Exposure
N. Zhang (2015)
10.4103/1008-682X.153303
Redox regulation of mammalian sperm capacitation
C. O'Flaherty (2015)
10.1016/c2014-0-02761-x
Emerging Trends in Computational Biology, Bioinformatics, and Systems Biology: Algorithms and Software Tools
A. R. Hamid (2015)
10.7314/APJCP.2015.16.1.23
FoxM1 as a novel therapeutic target for cancer drug therapy.
Xin-sen Xu (2015)
10.1007/s00432-015-1916-3
The functional role of peroxiredoxin 3 in reactive oxygen species, apoptosis, and chemoresistance of cancer cells
Lianqin Li (2015)
10.1371/journal.pone.0127310
Disabling Mitochondrial Peroxide Metabolism via Combinatorial Targeting of Peroxiredoxin 3 as an Effective Therapeutic Approach for Malignant Mesothelioma
B. Cunniff (2015)
10.1007/978-3-319-06068-2_21
Thiostrepton, a natural compound that triggers heat shock response and apoptosis in human cancer cells: a proteomics investigation.
C. Sandu (2014)
10.3892/ijo.2014.2304
Gentian violet induces wtp53 transactivation in cancer cells
A. Garufi (2014)
10.1007/978-3-642-30018-9_201
Asbestos-Induced Oxidative Stress in Lung Pathogenesis
Jill M. Miller (2014)
10.1016/j.redox.2014.01.021
Resolution of oxidative stress by thioredoxin reductase: Cysteine versus selenocysteine
B. Cunniff (2014)
Mitochondrial structure and function as a therapeutic target in malignant mesothelioma
Brian Cunnfff (2014)
10.1101/005942
Copy number networks to guide combinatorial therapy for cancer and other disorders
A. Lin (2014)
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