The potential for citrate to reinforce epigenetic therapy by promoting apoptosis

Philippe Icard; Marco Alifano; Luca Simula

doi:10.1016/j.tem.2023.07.002

The potential for citrate to reinforce epigenetic therapy by promoting apoptosis

Trends Endocrinol Metab. 2023 Oct;34(10):586-589. doi: 10.1016/j.tem.2023.07.002. Epub 2023 Aug 5.

Authors

Philippe Icard¹, Marco Alifano², Luca Simula³

Affiliations

¹ Normandie 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. Electronic address: philippe.icard@aphp.fr.
² Service de Chirurgie Thoracique, Hôpital Cochin, Hôpitaux Universitaires Paris Centre, APHP, Université Paris-Descartes, Paris, France; INSERM U1138, Integrative Cancer Immunology, University of Paris, 75006 Paris, France.
³ Cochin Institute, INSERM U1016, CNRS UMR8104, University of Paris-Cité, Paris, 75014, France.

PMID: 37550099
DOI: 10.1016/j.tem.2023.07.002

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).

Keywords: Warburg effect; apoptosis; citrate; drug resistance; epigenetic drug; necroptosis.

MeSH terms

Adenosine Triphosphate
Apoptosis / genetics
Citrates / pharmacology
Citric Acid* / pharmacology
Epigenesis, Genetic / genetics
Humans
Neoplasms* / drug therapy
Neoplasms* / genetics
bcl-X Protein / genetics
bcl-X Protein / metabolism
bcl-X Protein / pharmacology

Substances

Citric Acid
bcl-X Protein
Citrates
Adenosine Triphosphate