Anticancer Activity of the Choline Kinase Inhibitor PL48 Is Due to Selective Disruption of Choline Metabolism and Transport Systems in Cancer Cell Lines García Molina, Pablo Sola Leyva, Alberto Luque Navarro, Pilar María Laso, Alejandro Ríos Marco, Pablo Ríos Guadix, Antonio López Cara, Luisa Carlota Marco De La Calle, Carmen Carrasco Jiménez, María Paz Cancer Lipid metabolism Choline kinase inhibitors Choline uptake This research work was supported by Ministerio de Ciencia e Innovacion (PID2019-109294RB-100) Project. This research was also aided by the Andalusian regional government (CTS-236), B-CTS-216-UGR20 project and by the University of Perugia. Alberto Sola-Leyva holds a Formacion de Doctores 2018 grant (ref. PRE2018-085440) from the Ministerio de Ciencia, Innovacion y Universidades (Spain). Pilar M. Luque-Navarro holds a grant from Ministero dellIstruzione (Italy). Emilio Parisini acknowledges the European Regional Development Fund (ERDF) project BioDrug (No. 1.1.1.5/19/A/004) and the Latvian Council of Science (grant No. lzp-2020/2-0013) for financial support. 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. 2022-03-28T11:06:14Z 2022-03-28T11:06:14Z 2022-02-16 journal article García-Molina, P... [et al.]. Anticancer Activity of the Choline Kinase Inhibitor PL48 Is Due to Selective Disruption of Choline Metabolism and Transport Systems in Cancer Cell Lines. Pharmaceutics 2022, 14, 426. [https://doi.org/10.3390/pharmaceutics14020426] http://hdl.handle.net/10481/73840 10.3390/pharmaceutics14020426 eng http://creativecommons.org/licenses/by/3.0/es/ open access Atribución 3.0 España MDPI