@misc{10481/73840,
year = {2022},
month = {2},
url = {http://hdl.handle.net/10481/73840},
abstract = {A large number of different types of cancer have been shown to be associated with an abnormal metabolism of phosphatidylcholine (PC), the main component of eukaryotic cell membranes. Indeed, the overexpression of choline kinase alpha 1 (ChoK alpha 1), the enzyme that catalyses the bioconversion of choline to phosphocholine (PCho), has been found to associate with cell proliferation, oncogenic transformation and carcinogenesis. Hence, ChoK alpha 1 has been described as a possible cancer therapeutic target. Moreover, the choline transporter CTL1 has been shown to be highly expressed in several tumour cell lines. In the present work, we evaluate the antiproliferative effect of PL48, a rationally designed inhibitor of ChoK alpha 1, in MCF7 and HepG2 cell lines. In addition, we illustrate that the predominant mechanism of cellular choline uptake in these cells is mediated by the CTL1 choline transporter. A possible correlation between the inhibition of both choline uptake and ChoK alpha 1 activity and cell proliferation in cancer cell lines is also highlighted. We conclude that the efficacy of this inhibitor on cell proliferation in both cell lines is closely correlated with its capability to block choline uptake and ChoK alpha 1 activity, making both proteins potential targets in cancer therapy.},
organization = {Instituto de Salud Carlos III},
organization = {Spanish Government},
organization = {European Commission	PID2019-109294RB-100},
organization = {Andalusian regional government	CTS-236	
B-CTS-216-UGR20},
organization = {Spanish Government	PRE2018-085440},
organization = {European Regional Development Fund (ERDF) project BioDrug	1.1.1.5/19/A/004},
organization = {Latvian Ministry of Education and Science	lzp-2020/2-0013},
publisher = {MDPI},
keywords = {Cancer},
keywords = {Lipid metabolism},
keywords = {Choline kinase inhibitors},
keywords = {Choline uptake},
title = {Anticancer Activity of the Choline Kinase Inhibitor PL48 Is Due to Selective Disruption of Choline Metabolism and Transport Systems in Cancer Cell Lines},
doi = {10.3390/pharmaceutics14020426},
author = {García Molina, Pablo and Sola Leyva, Alberto and Luque Navarro, Pilar María and Laso, Alejandro and Ríos Marco, Pablo and Ríos Guadix, Antonio and López Cara, Luisa Carlota and Marco De La Calle, Carmen and Carrasco Jiménez, María Paz},
}