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Cell Cycle. 2017 Feb;16(3):271-279. doi: 10.1080/15384101.2016.1249550. Epub 2017 Jan 6.

Metabolic interactions between cysteamine and epigallocatechin gallate.

Izzo V1,2,3,4, Pietrocola F1,2,3,4, Sica V1,2,3,4,5, Durand S1,2,3,4, Lachkar S1,2,3,4, Enot D1,2,3,4, Bravo-San Pedro JM1,2,3,4, Chery A1,2,3,4, Esposito S6, Raia V7, Maiuri L6,8, Maiuri MC1,2,3,4, Kroemer G1,2,3,4,9,10.

Author information

1
a Equipe 11 labellisée Ligue contre le Cancer, Centre de Recherche des Cordeliers , INSERM U 1138, Paris , France.
2
b Université Paris Descartes, Sorbonne Paris Cité , Paris , France.
3
c Université Pierre et Marie Curie , Paris , France.
4
d Metabolomics and Cell Biology Platforms, Gustave Roussy Comprehensive Cancer Institute , Villejuif , France.
5
e Université Paris Sud, Faculté de Médecine , Kremlin Bicêtre , France.
6
f European Institute for Research in Cystic Fibrosis, Division of Genetics and Cell Biology, San Raffaele Scientific Institute , Milan , Italy.
7
g Regional Cystic Fibrosis Center, Pediatric Unit, Department of Translational Medical Sciences , Federico II University , Naples , Italy.
8
h SCDU of Pediatrics, Department of Health Sciences , University of Piemonte Orientale , Novara , Italy.
9
i Pôle de Biologie, Hôpital Européen Georges Pompidou, AP-HP , Paris , France.
10
j Karolinska Institute, Department of Women's and Children's Health , Karolinska University Hospital , Stockholm , Sweden.

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.

KEYWORDS:

EP300; acetylation; cysteamine; cystic fibrosis; epigallocatechin gallate; metabolic flux; metabolic profiling

PMID:
28059601
PMCID:
PMC5323035
DOI:
10.1080/15384101.2016.1249550
[Indexed for MEDLINE]
Free PMC Article

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