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dc.contributor.authorSola Leyva, Alberto 
dc.contributor.authorLópez Cara, Luisa Carlota 
dc.contributor.authorRíos Guadix, Antonio 
dc.contributor.authorRíos Marco, Pablo
dc.contributor.authorMarco De La Calle, Carmen 
dc.contributor.authorCarrasco Jiménez, María Paz 
dc.date.accessioned2020-05-06T12:03:45Z
dc.date.available2020-05-06T12:03:45Z
dc.date.issued2019-03-25
dc.identifier.citationSola-Leyva, A., López-Cara, L. C., Ríos-Marco, P., Ríos, A., Marco, C., & Carrasco-Jiménez, M. P. (2019). Choline kinase inhibitors EB-3D and EB-3P interferes with lipid homeostasis in HepG2 cells. Scientific reports, 9(1), 1-13.es_ES
dc.identifier.urihttp://hdl.handle.net/10481/61841
dc.description.abstractA full understanding of the molecular mechanism of action of choline kinase α (ChoKα) inhibitors at the cell level is essential for developing therapeutic and preventive approaches for cancer. The aim of the present study was to evaluate the effects of the ChoKα inhibitors EB-3D and EB-3P on lipid metabolism in HepG2 cells. We used [methyl-14C]choline, [1,2-14C]acetic acid and [2-3H]glycerol as exogenous precursors of the corresponding phospholipids and neutral lipids. [Methyl-14C]choline was also used to determine choline uptake. Protein levels were determined by Western blot. Ultrastructural alterations were investigated by transmission electron microscopy. In this work, we demonstrate that EB-3D and EB-3P interfere with phosphatidylcholine biosynthesis via both CDP-choline pathway and choline uptake by the cell. Moreover, the synthesis of both diacylglycerols and triacylglycerols was affected by cell exposure to both inhibitors. These effects were accompanied by a substantial decrease in cholesterol biosynthesis, as well as alterations in the expression of proteins related to cholesterol homeostasis. We also found that EB-3D and EB-3P lowered ChoKα protein levels. All these effects could be explained by the modulation of the AMP-activated protein kinase signalling pathway. We show that both inhibitors cause mitochondrial alteration and an endoplasmic reticulum stress response. EB-3D and EB-3P exert effects on ChoKα expression, AMPK activation, apoptosis, endoplasmic reticulum stress and lipid metabolism. Taken together, results show that EB-3D and EB-3P have potential anticancer activity through the deregulation of lipid metabolism.es_ES
dc.description.sponsorshipThis work was aided by the Andalusian Regional Government (P11-CVI-7859). The inhibitors were developed under the Cei-Biotic Project CEI2013-MP-1 (University of Granada).es_ES
dc.language.isoenges_ES
dc.publisherSpringer Naturees_ES
dc.rightsAtribución 3.0 España*
dc.rights.urihttp://creativecommons.org/licenses/by/3.0/es/*
dc.titleCholine kinase inhibitors EB-3D and EB-3P interferes with lipid homeostasis in HepG2 cellses_ES
dc.typeinfo:eu-repo/semantics/articlees_ES
dc.rights.accessRightsinfo:eu-repo/semantics/openAccesses_ES
dc.identifier.doi10.1038/s41598-019-40885-z


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