Metabolic interactions between cysteamine and epigallocatechin gallate.

Cell cycle (Georgetown, Tex.) (2017-01-07)
Valentina Izzo, Federico Pietrocola, Valentina Sica, Sylvère Durand, Sylvie Lachkar, David Enot, José Manuel Bravo-San Pedro, Alexis Chery, Speranza Esposito, Valeria Raia, Luigi Maiuri, Maria Chiara Maiuri, Guido Kroemer
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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Earle′s Balanced Salts, With sodium bicarbonate, liquid, sterile-filtered, suitable for cell culture
Supelco
Dibutylammonium acetate solution, 0.5 M in H2O, LiChropur, suitable for ion pair chromatography
Sigma-Aldrich
Nα-Acetyl-L-lysine
Sigma-Aldrich
Anacardic acid