Cystathionine gamma-lyase (CTH) inhibition attenuates glioblastoma formation.

Mice Humans Animals Glioblastoma / drug therapy Cystathionine gamma-Lyase / genetics Mice, Inbred C57BL Temozolomide Cell Line Cell Line, Tumor
Brain blood vessels Cystathionine gamma-lyase (CTH) Glioblastoma stem cells (GSC) Sex determining region Y-Box 2 (SOX2)

Journal

Redox biology
ISSN: 2213-2317
Titre abrégé: Redox Biol
Pays: Netherlands
ID NLM: 101605639

Informations de publication

Date de publication:
08 2023
Historique:
received: 06 05 2023
accepted: 03 06 2023
medline: 12 7 2023
pubmed: 11 6 2023
entrez: 10 6 2023
Statut: ppublish

Résumé

Glioblastoma (GBM) is the most common type of adult brain tumor with extremely poor survival. Cystathionine-gamma lyase (CTH) is one of the main Hydrogen Sulfide (H and Principal Results: An established allogenic immunocompetent in vivo GBM model was used in C57BL/6J WT and CTH KO mice where the tumor volume and tumor microvessel density were blindly measured by stereological analysis. Tumor macrophage and stemness markers were measured by blinded immunohistochemistry. Mouse and human GBM cell lines were used for cell-based analyses. In human gliomas, the CTH expression was analyzed by bioinformatic analysis on different databases. In vivo, the genetic ablation of CTH in the host led to a significant reduction of the tumor volume and the protumorigenic and stemness transcription factor sex determining region Y-box 2 (SOX2). The tumor microvessel density (indicative of angiogenesis) and the expression levels of peritumoral macrophages showed no significant changes between the two genotypes. Bioinformatic analysis in human glioma tumors revealed that higher CTH expression is positively correlated to SOX2 expression and associated with worse overall survival in all grades of gliomas. Patients not responding to temozolomide have also higher CTH expression. In mouse or human GBM cells, pharmacological inhibition (PAG) or CTH knockdown (siRNA) attenuates GBM cell proliferation, migration and stem cell formation frequency. Inhibition of CTH could be a new promising target against glioblastoma formation.

Identifiants

DOI: 10.1016/j.redox.2023.102773 PMID: 37300955 PMC: PMC10363444
pubmed: 37300955
pii: S2213-2317(23)00174-X
doi: 10.1016/j.redox.2023.102773
pmc: PMC10363444
pii:
doi:

Substances chimiques

Cystathionine gamma-Lyase EC 4.4.1.1
Temozolomide YF1K15M17Y

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

102773

Informations de copyright

Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of competing interest The authors declare no conflict of interest.

Références

EBioMedicine. 2015 Aug 15;2(10):1351-63
pubmed: 26629530
J Immunol Methods. 2009 Aug 15;347(1-2):70-8
pubmed: 19567251
Stroke Vasc Neurol. 2021 Jun;6(2):244-251
pubmed: 33246971
EMBO Rep. 2019 Oct 4;20(10):e45986
pubmed: 31468690
Cancer Immunol Res. 2020 Jul;8(7):966-981
pubmed: 32350000
Nat Rev Drug Discov. 2016 Mar;15(3):185-203
pubmed: 26678620
Curr Pharm Des. 2021;27(46):4650-4662
pubmed: 34397322
Neoplasia. 2014 Mar;16(3):193-206, 206.e19-25
pubmed: 24726753
Sci Signal. 2013 Apr 02;6(269):pl1
pubmed: 23550210
J Am Soc Nephrol. 2010 Mar;21(3):448-59
pubmed: 20056745
Oxid Med Cell Longev. 2021 Jun 27;2021:5549047
pubmed: 34257808
Neuro Oncol. 2014 Dec;16(12):1575-84
pubmed: 25082799
J Cell Physiol. 2022 Jan;237(1):743-762
pubmed: 34350982
Int J Mol Sci. 2022 May 06;23(9):
pubmed: 35563591
JAMA Oncol. 2022 Oct 1;8(10):1493-1501
pubmed: 36006639
Int J Oncol. 2019 Aug;55(2):473-487
pubmed: 31173185
J Neurooncol. 2014 May;118(1):1-8
pubmed: 24522719
J Am Soc Nephrol. 1999 May;10(5):1100-23
pubmed: 10232698
Stem Cells. 2009 Jan;27(1):40-8
pubmed: 18948646
APMIS. 1988 May;96(5):379-94
pubmed: 3288247
Neurosurg Clin N Am. 2012 Jul;23(3):391-405
pubmed: 22748652
Nucleic Acids Res. 2019 Jul 2;47(W1):W556-W560
pubmed: 31114875
Genomics Proteomics Bioinformatics. 2021 Feb;19(1):1-12
pubmed: 33662628
PLoS One. 2016 Sep 01;11(9):e0161496
pubmed: 27583442
Int J Mol Sci. 2020 Oct 06;21(19):
pubmed: 33036204
Nat Protoc. 2007;2(2):329-33
pubmed: 17406593
Acta Physiol (Oxf). 2022 Aug;235(4):e13828
pubmed: 35543087
Mol Oncol. 2022 May;16(9):1891-1912
pubmed: 35203105
Carcinogenesis. 2021 Jun 21;42(6):804-813
pubmed: 33754151
Sci Signal. 2015 Dec 08;8(406):ra125
pubmed: 26645582
J Biol Chem. 2006 Nov 24;281(47):35785-93
pubmed: 17005561
Curr Pharm Des. 2011;17(23):2386-401
pubmed: 21827414
Proc Natl Acad Sci U S A. 2009 Dec 22;106(51):21972-7
pubmed: 19955410
Pol J Pathol. 2003;54(4):249-52
pubmed: 14998293
Mol Cancer Res. 2014 Oct;12(10):1398-406
pubmed: 24994751
Eur J Immunol. 1994 Jan;24(1):216-21
pubmed: 8020558
Br J Cancer. 1994 Aug;70(2):199-203
pubmed: 8054266
Neuro Oncol. 2017 Oct 19;19(11):1435-1446
pubmed: 28575312
CNS Oncol. 2016 Jul;5(3):159-73
pubmed: 27230973
Cancer Cell. 2015 Feb 9;27(2):156-7
pubmed: 25670075
J Neurooncol. 2004 Mar-Apr;67(1-2):77-81
pubmed: 15072451
Pharmacol Rev. 2017 Oct;69(4):497-564
pubmed: 28978633
Mol Biol Cell. 2018 Oct 15;29(21):2509-2515
pubmed: 30325290
Neurooncol Adv. 2021 Apr 09;3(1):vdab057
pubmed: 34250481
J Clin Invest. 2021 Jul 13;:
pubmed: 34255747
Expert Rev Anticancer Ther. 2017 Jun;17(6):507-515
pubmed: 28438066
Cell Death Dis. 2022 Oct 30;13(10):913
pubmed: 36310164
Pharmacol Rev. 2018 Jul;70(3):412-445
pubmed: 29669750
Int J Cancer. 2019 Dec 1;145(11):3140-3151
pubmed: 31020993
N Engl J Med. 2005 Mar 10;352(10):987-96
pubmed: 15758009
Nat Rev Neurosci. 2011 Aug 03;12(9):495-508
pubmed: 21811295
Antioxidants (Basel). 2021 Jun 17;10(6):
pubmed: 34204425
Genes Dev. 2015 Jun 15;29(12):1203-17
pubmed: 26109046

Auteurs

Maria Peleli (M)

Department of Medical Biochemistry and Microbiology, Science for Life Laboratory, Uppsala University, Box 582, SE-751 23, Uppsala, Sweden; Clinical, Experimental Surgery and Translational Research Center, Biomedical Research Foundation of the Academy of Athens, Athens, Greece; Department of Cardiovascular and Renal Research, Institute of Molecular Medicine, University of Southern Denmark, J. B. Winslowsvej 21, 3, 5000, Odense C, Denmark.

Ivi Antoniadou (I)

Clinical, Experimental Surgery and Translational Research Center, Biomedical Research Foundation of the Academy of Athens, Athens, Greece; Laboratory of Pharmacology, Department of Pharmacy, National and Kapodistrian University of Athens, Athens, Greece.

Dorival Mendes Rodrigues-Junior (DM)

Department of Medical Biochemistry and Microbiology, Science for Life Laboratory, Uppsala University, Box 582, SE-751 23, Uppsala, Sweden.

Odysseia Savvoulidou (O)

Department of Cardiovascular and Renal Research, Institute of Molecular Medicine, University of Southern Denmark, J. B. Winslowsvej 21, 3, 5000, Odense C, Denmark.

Laia Caja (L)

Department of Medical Biochemistry and Microbiology, Science for Life Laboratory, Uppsala University, Box 582, SE-751 23, Uppsala, Sweden.

Antonia Katsouda (A)

Clinical, Experimental Surgery and Translational Research Center, Biomedical Research Foundation of the Academy of Athens, Athens, Greece; Laboratory of Pharmacology, Department of Pharmacy, National and Kapodistrian University of Athens, Athens, Greece.

Daniel F J Ketelhuth (DFJ)

Department of Cardiovascular and Renal Research, Institute of Molecular Medicine, University of Southern Denmark, J. B. Winslowsvej 21, 3, 5000, Odense C, Denmark; Division of Cardiovascular Medicine, Center for Molecular Medicine, Department of Medicine, Karolinska Institute, Karolinska University Hospital, Stockholm, Sweden.

Jane Stubbe (J)

Department of Cardiovascular and Renal Research, Institute of Molecular Medicine, University of Southern Denmark, J. B. Winslowsvej 21, 3, 5000, Odense C, Denmark.

Kirsten Madsen (K)

Department of Cardiovascular and Renal Research, Institute of Molecular Medicine, University of Southern Denmark, J. B. Winslowsvej 21, 3, 5000, Odense C, Denmark; Department of Pathology, Odense University Hospital, J.B Winslowsvej 15, 5000, Odense C, Denmark.

Aristidis Moustakas (A)

Department of Medical Biochemistry and Microbiology, Science for Life Laboratory, Uppsala University, Box 582, SE-751 23, Uppsala, Sweden. Electronic address: aris.moustakas@imbim.uu.se.

Andreas Papapetropoulos (A)

Clinical, Experimental Surgery and Translational Research Center, Biomedical Research Foundation of the Academy of Athens, Athens, Greece; Laboratory of Pharmacology, Department of Pharmacy, National and Kapodistrian University of Athens, Athens, Greece. Electronic address: apapapet@pharm.uoa.gr.

Articles similaires

[Redispensing of expensive oral anticancer medicines: a practical application].

Lisanne N van Merendonk, Kübra Akgöl, Bastiaan Nuijen
1.00
Humans Antineoplastic Agents Administration, Oral Drug Costs Counterfeit Drugs

Smoking Cessation and Incident Cardiovascular Disease.

Jun Hwan Cho, Seung Yong Shin, Hoseob Kim et al.
1.00
Humans Male Smoking Cessation Cardiovascular Diseases Female

Evaluation of Low-Value Services Across Major Medicare Advantage Insurers and Traditional Medicare.

Ciara Duggan, Adam L Beckman, Ishani Ganguli et al.
1.00
Humans United States Aged Cross-Sectional Studies Medicare Part C

Effectiveness of Virtual Yoga for Chronic Low Back Pain: A Randomized Clinical Trial.

Hallie Tankha, Devyn Gaskins, Amanda Shallcross et al.
1.00
Humans Yoga Low Back Pain Female Male

Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Cystathionine gamma-lyase (CTH) inhibition...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Cystathionine gamma-lyase (CTH) inhibition...
questionsmedicales.fr › Eucaryotes › Animaux › Cystathionine gamma-lyase (CTH) inhibition...
questionsmedicales.fr › Tumeurs › Tumeurs par type histologique › Tumeurs du tissu nerveux › Tumeurs neuroectodermiques › Tumeurs neuroépitheliales › Gliome › Astrocytome › Glioblastome › Cystathionine gamma-lyase (CTH) inhibition...
questionsmedicales.fr › Enzymes et coenzymes › Enzymes › Lyases › Carbon-sulfur lyases › Cystathionine gamma-lyase › Cystathionine gamma-lyase (CTH) inhibition...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Lignées consanguines de souris › Souris de lignée C57BL › Cystathionine gamma-lyase (CTH) inhibition...
questionsmedicales.fr › Composés hétérocycliques › Composés hétéromonocycliques › Azoles › Imidazoles › Dacarbazine › Témozolomide › Cystathionine gamma-lyase (CTH) inhibition...
questionsmedicales.fr › Cellules › Cellules cultivées › Lignée cellulaire › Cystathionine gamma-lyase (CTH) inhibition...
questionsmedicales.fr › Cellules › Cellules cultivées › Cellules cancéreuses en culture › Lignée cellulaire tumorale › Cystathionine gamma-lyase (CTH) inhibition...