title: Metabolic interactions between cysteamine and epigallocatechin gallate.
abstract: Phase II clinical trials indicate that the combination of cysteamine plus epigallocatechin gallate (EGCG) is effective against cystic fibrosis in patients bearing the most frequent etiological mutation (CFTRΔF508). Here, we investigated the interaction between both agents on cultured respiratory epithelia cells from normal and CFTRΔF508-mutated donors. We observed that the combination of both agents affected metabolic circuits (and in particular the tricarboxylic acid cycle) in a unique way and that cysteamine plus EGCG reduced cytoplasmic protein acetylation more than each of the 2 components alone. In a cell-free system, protein cross-linking activity of EGCG was suppressed by cysteamine. Finally, EGCG was able to enhance the conversion of cysteamine into taurine in metabolic flux experiments. Altogether, these results indicate that multiple pharmacological interactions occur between cysteamine and EGCG, suggesting that they contribute to the unique synergy of both agents in restoring the function of mutated CFTRΔF508.
authors.affiliation: a Equipe 11 labellisée Ligue contre le Cancer, Centre de Recherche des Cordeliers , INSERM U 1138, Paris , France.|b Université Paris Descartes, Sorbonne Paris Cité , Paris , France.|c Université Pierre et Marie Curie , Paris , France.|d Metabolomics and Cell Biology Platforms, Gustave Roussy Comprehensive Cancer Institute , Villejuif , France.
authors.forename: Valentina
authors.initials: V
authors.lastname: Izzo
authors.affiliation: a Equipe 11 labellisée Ligue contre le Cancer, Centre de Recherche des Cordeliers , INSERM U 1138, Paris , France.|b Université Paris Descartes, Sorbonne Paris Cité , Paris , France.|c Université Pierre et Marie Curie , Paris , France.|d Metabolomics and Cell Biology Platforms, Gustave Roussy Comprehensive Cancer Institute , Villejuif , France.
authors.forename: Federico
authors.initials: F
authors.lastname: Pietrocola
authors.affiliation: a Equipe 11 labellisée Ligue contre le Cancer, Centre de Recherche des Cordeliers , INSERM U 1138, Paris , France.|b Université Paris Descartes, Sorbonne Paris Cité , Paris , France.|c Université Pierre et Marie Curie , Paris , France.|d Metabolomics and Cell Biology Platforms, Gustave Roussy Comprehensive Cancer Institute , Villejuif , France.|e Université Paris Sud, Faculté de Médecine , Kremlin Bicêtre , France.
authors.forename: Valentina
authors.initials: V
authors.lastname: Sica
authors.affiliation: a Equipe 11 labellisée Ligue contre le Cancer, Centre de Recherche des Cordeliers , INSERM U 1138, Paris , France.|b Université Paris Descartes, Sorbonne Paris Cité , Paris , France.|c Université Pierre et Marie Curie , Paris , France.|d Metabolomics and Cell Biology Platforms, Gustave Roussy Comprehensive Cancer Institute , Villejuif , France.
authors.forename: Sylvère
authors.initials: S
authors.lastname: Durand
authors.affiliation: a Equipe 11 labellisée Ligue contre le Cancer, Centre de Recherche des Cordeliers , INSERM U 1138, Paris , France.|b Université Paris Descartes, Sorbonne Paris Cité , Paris , France.|c Université Pierre et Marie Curie , Paris , France.|d Metabolomics and Cell Biology Platforms, Gustave Roussy Comprehensive Cancer Institute , Villejuif , France.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Lachkar
authors.affiliation: a Equipe 11 labellisée Ligue contre le Cancer, Centre de Recherche des Cordeliers , INSERM U 1138, Paris , France.|b Université Paris Descartes, Sorbonne Paris Cité , Paris , France.|c Université Pierre et Marie Curie , Paris , France.|d Metabolomics and Cell Biology Platforms, Gustave Roussy Comprehensive Cancer Institute , Villejuif , France.
authors.forename: David
authors.initials: D
authors.lastname: Enot
authors.affiliation: a Equipe 11 labellisée Ligue contre le Cancer, Centre de Recherche des Cordeliers , INSERM U 1138, Paris , France.|b Université Paris Descartes, Sorbonne Paris Cité , Paris , France.|c Université Pierre et Marie Curie , Paris , France.|d Metabolomics and Cell Biology Platforms, Gustave Roussy Comprehensive Cancer Institute , Villejuif , France.
authors.forename: José Manuel
authors.initials: JM
authors.lastname: Bravo-San Pedro
authors.affiliation: a Equipe 11 labellisée Ligue contre le Cancer, Centre de Recherche des Cordeliers , INSERM U 1138, Paris , France.|b Université Paris Descartes, Sorbonne Paris Cité , Paris , France.|c Université Pierre et Marie Curie , Paris , France.|d Metabolomics and Cell Biology Platforms, Gustave Roussy Comprehensive Cancer Institute , Villejuif , France.
authors.forename: Alexis
authors.initials: A
authors.lastname: Chery
authors.affiliation: f European Institute for Research in Cystic Fibrosis, Division of Genetics and Cell Biology, San Raffaele Scientific Institute , Milan , Italy.
authors.forename: Speranza
authors.initials: S
authors.lastname: Esposito
authors.affiliation: g Regional Cystic Fibrosis Center, Pediatric Unit, Department of Translational Medical Sciences , Federico II University , Naples , Italy.
authors.forename: Valeria
authors.initials: V
authors.lastname: Raia
authors.affiliation: f European Institute for Research in Cystic Fibrosis, Division of Genetics and Cell Biology, San Raffaele Scientific Institute , Milan , Italy.|h SCDU of Pediatrics, Department of Health Sciences , University of Piemonte Orientale , Novara , Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: Maiuri
authors.affiliation: a Equipe 11 labellisée Ligue contre le Cancer, Centre de Recherche des Cordeliers , INSERM U 1138, Paris , France.|b Université Paris Descartes, Sorbonne Paris Cité , Paris , France.|c Université Pierre et Marie Curie , Paris , France.|d Metabolomics and Cell Biology Platforms, Gustave Roussy Comprehensive Cancer Institute , Villejuif , France.
authors.forename: Maria Chiara
authors.initials: MC
authors.lastname: Maiuri
authors.affiliation: a Equipe 11 labellisée Ligue contre le Cancer, Centre de Recherche des Cordeliers , INSERM U 1138, Paris , France.|b Université Paris Descartes, Sorbonne Paris Cité , Paris , France.|c Université Pierre et Marie Curie , Paris , France.|d Metabolomics and Cell Biology Platforms, Gustave Roussy Comprehensive Cancer Institute , Villejuif , France.|i Pôle de Biologie, Hôpital Européen Georges Pompidou, AP-HP , Paris , France.|j Karolinska Institute, Department of Women's and Children's Health , Karolinska University Hospital , Stockholm , Sweden.
authors.forename: Guido
authors.initials: G
authors.lastname: Kroemer
mesh_terms: D000107:Acetylation / Q000187:drug effects; D002392:Catechin / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D002460:Cell Line; D002952:Citric Acid Cycle / Q000187:drug effects; D003432:Cross-Linking Reagents / Q000378:metabolism; D003543:Cysteamine / Q000378:metabolism* / Q000494:pharmacology; D003593:Cytoplasm / Q000378:metabolism; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D064688:Metabolic Flux Analysis; D055432:Metabolomics; D020545:Respiratory Mucosa / Q000166:cytology
chemical_list: D003432:Cross-Linking Reagents; D003543:Cysteamine; D002392:Catechin; C045651:epigallocatechin gallate
keywords: EP300; acetylation; cysteamine; cystic fibrosis; epigallocatechin gallate; metabolic flux; metabolic profiling