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PubMed

Záznam pochází z PubMed

Metformin regulates global DNA methylation via mitochondrial one-carbon metabolism

Cuyàs, E
Autor Cuyàs, E ProCURE (Program Against Cancer Therapeutic Resistance), Metabolism & Cancer Group, Catalan Institute of Oncology, Girona, Catalonia, Spain Girona Biomedical Research Institute (IDIBGI), Girona, Catalonia, Spain
Fernández-Arroyo, S
Autor Fernández-Arroyo, S Unitat de Recerca Biomèdica, Hospital Universitari Sant Joan, Institut d'Investigació Sanitària Pere Virgili, Universitat Rovira i Virgili, Reus, Spain The Campus of International Excellence Southern Catalonia, Tarragona, Spain
Verdura, S
Autor Verdura, S ProCURE (Program Against Cancer Therapeutic Resistance), Metabolism & Cancer Group, Catalan Institute of Oncology, Girona, Catalonia, Spain Girona Biomedical Research Institute (IDIBGI), Girona, Catalonia, Spain
García, R Á-F
Autor García, R Á-F Department of Physical and Analytical Chemistry, Faculty of Chemistry, University of Oviedo, Oviedo, Spain
Stursa, J
Autor Stursa, J Institute of Chemical Technology, Prague, Czech Republic Institute of Biotechnology, Czech Academy of Sciences, Prague-West, Czech Republic
Werner, L
Autor Werner, L Institute of Chemical Technology, Prague, Czech Republic Institute of Biotechnology, Czech Academy of Sciences, Prague-West, Czech Republic
Blanco-González, E
Autor Blanco-González, E Department of Physical and Analytical Chemistry, Faculty of Chemistry, University of Oviedo, Oviedo, Spain
Montes-Bayón, M
Autor Montes-Bayón, M Department of Physical and Analytical Chemistry, Faculty of Chemistry, University of Oviedo, Oviedo, Spain
Joven, J
Autor Joven, J Unitat de Recerca Biomèdica, Hospital Universitari Sant Joan, Institut d'Investigació Sanitària Pere Virgili, Universitat Rovira i Virgili, Reus, Spain The Campus of International Excellence Southern Catalonia, Tarragona, Spain
Viollet, B
Autor Viollet, B INSERM U1016, Institut Cochin, Paris, France CNRS UMR 8104, Paris, France Université Paris Descartes, Sorbonne Paris Cité, Paris, France
Neuzil, J
Autor Neuzil, J Institute of Chemical Technology, Prague, Czech Republic School of Medical Science, Griffith University, Southport, Queensland, Australia
Menendez, J A
Autor Menendez, J A ProCURE (Program Against Cancer Therapeutic Resistance), Metabolism & Cancer Group, Catalan Institute of Oncology, Girona, Catalonia, Spain Girona Biomedical Research Institute (IDIBGI), Girona, Catalonia, Spain

Oncogene. 2018 Feb 15 ; 37 (7) : 963-970. [epub] 20171023

ISSN 1476-5594 | 0950-9232
Zdroj

Jazyk angličtina Země Velká Británie, Anglie Médium print-electronic

Typ dokumentu časopisecké články, práce podpořená grantem

Perzistentní odkaz https://www.medvik.cz/link/pmid29059169

PubMed 29059169
DOI 10.1038/onc.2017.367
PII: onc2017367
Knihovny.cz E-zdroje

MeSH
genom lidský * MeSH
hypoglykemika farmakologie MeSH
lidé MeSH
metformin farmakologie MeSH
metylace DNA účinky léků MeSH
mitochondrie účinky léků metabolismus patologie MeSH
myši MeSH
nádorové biomarkery MeSH
nádorové buňky kultivované MeSH
nádory prsu farmakoterapie enzymologie patologie MeSH
nádory tračníku farmakoterapie enzymologie patologie MeSH
následné studie MeSH
proteinkinasy aktivované AMP metabolismus MeSH
regulace genové exprese u nádorů účinky léků MeSH
respirační komplex I metabolismus MeSH
S-adenosylhomocystein metabolismus MeSH
S-adenosylmethionin metabolismus MeSH
uhlík metabolismus MeSH
zvířata MeSH
Check Tag
lidé MeSH
myši MeSH
ženské pohlaví MeSH
zvířata MeSH
Publikační typ
časopisecké články MeSH
práce podpořená grantem MeSH
Názvy látek
hypoglykemika MeSH
metformin MeSH
nádorové biomarkery MeSH
proteinkinasy aktivované AMP MeSH
respirační komplex I MeSH
S-adenosylhomocystein MeSH
S-adenosylmethionin MeSH
uhlík MeSH

The anti-diabetic biguanide metformin may exert health-promoting effects via metabolic regulation of the epigenome. Here we show that metformin promotes global DNA methylation in non-cancerous, cancer-prone and metastatic cancer cells by decreasing S-adenosylhomocysteine (SAH), a strong feedback inhibitor of S-adenosylmethionine (SAM)-dependent DNA methyltransferases, while promoting the accumulation of SAM, the universal methyl donor for cellular methylation. Using metformin and a mitochondria/complex I (mCI)-targeted analog of metformin (norMitoMet) in experimental pairs of wild-type and AMP-activated protein kinase (AMPK)-, serine hydroxymethyltransferase 2 (SHMT2)- and mCI-null cells, we provide evidence that metformin increases the SAM:SAH ratio-related methylation capacity by targeting the coupling between serine mitochondrial one-carbon flux and CI activity. By increasing the contribution of one-carbon units to the SAM from folate stores while decreasing SAH in response to AMPK-sensed energetic crisis, metformin can operate as a metabolo-epigenetic regulator capable of reprogramming one of the key conduits linking cellular metabolism to the DNA methylation machinery.

CNRS UMR 8104 Paris France

Department of Physical and Analytical Chemistry Faculty of Chemistry University of Oviedo Oviedo Spain

Girona Biomedical Research Institute Girona Catalonia Spain

INSERM U1016 Institut Cochin Paris France

Institute of Biotechnology Czech Academy of Sciences Prague West Czech Republic

Institute of Chemical Technology Prague Czech Republic

ProCURE Metabolism and Cancer Group Catalan Institute of Oncology Girona Catalonia Spain

School of Medical Science Griffith University Southport Queensland Australia

The Campus of International Excellence Southern Catalonia Tarragona Spain

Unitat de Recerca Biomèdica Hospital Universitari Sant Joan Institut d'Investigació Sanitària Pere Virgili Universitat Rovira i Virgili Reus Spain

Université Paris Descartes Sorbonne Paris Cité Paris France

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