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Updated: Jul 19, 2025

Repressing Gene Transcription by Redirecting Cellular Machinery with Chemical Epigenetic Modifiers
Published on: September 20, 2018
The potential for citrate to reinforce epigenetic therapy by promoting apoptosis
Philippe Icard1, Marco Alifano2, Luca Simula3
1Normandie University, UNICAEN, INSERM U1086 Interdisciplinary Research Unit for Cancer Prevention and Treatment, Caen, France; Service de Chirurgie Thoracique, Hôpital Cochin, Hôpitaux Universitaires Paris Centre, APHP, Université Paris-Descartes, Paris, France.
Abstract:
Epigenetic drugs induce ATP depletion, promoting a glycolysis-to-oxidative phosphorylation (OXPHOS) shift which sometimes favors tumor growth by promoting necroptosis over apoptosis. To restore effective apoptosis in tumors, we propose that the administration of citrate could inhibit ATP production, activate caspase-8 (a key necroptosis inhibitor), and downregulate key anti-apoptotic proteins (Bcl-xL and MCL1).
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