Anticancer Activity of the Choline Kinase Inhibitor PL48 Is Due to Selective Disruption of Choline Metabolism and Transport Systems in Cancer Cell Lines
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 α1 (ChoKα1), the enzyme that catalyses the bioconversion of choline to p...
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| Format: | Article |
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MDPI AG
2022-02-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/14/2/426 |
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| author | Pablo García-Molina Alberto Sola-Leyva Pilar M. Luque-Navarro Alejandro Laso Pablo Ríos-Marco Antonio Ríos Daniela Lanari Archimede Torretta Emilio Parisini Luisa C. López-Cara Carmen Marco María P. Carrasco-Jiménez |
| author_facet | Pablo García-Molina Alberto Sola-Leyva Pilar M. Luque-Navarro Alejandro Laso Pablo Ríos-Marco Antonio Ríos Daniela Lanari Archimede Torretta Emilio Parisini Luisa C. López-Cara Carmen Marco María P. Carrasco-Jiménez |
| author_sort | Pablo García-Molina |
| collection | DOAJ |
| description | 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 α1 (ChoKα1), the enzyme that catalyses the bioconversion of choline to phosphocholine (PCho), has been found to associate with cell proliferation, oncogenic transformation and carcinogenesis. Hence, ChoKα1 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 ChoKα1, 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 ChoKα1 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 ChoKα1 activity, making both proteins potential targets in cancer therapy. |
| first_indexed | 2024-03-09T21:13:53Z |
| format | Article |
| id | doaj.art-52feff0c502f4225b33e95e0ef1959fd |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-09T21:13:53Z |
| publishDate | 2022-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-52feff0c502f4225b33e95e0ef1959fd2023-11-23T21:39:11ZengMDPI AGPharmaceutics1999-49232022-02-0114242610.3390/pharmaceutics14020426Anticancer Activity of the Choline Kinase Inhibitor PL48 Is Due to Selective Disruption of Choline Metabolism and Transport Systems in Cancer Cell LinesPablo García-Molina0Alberto Sola-Leyva1Pilar M. Luque-Navarro2Alejandro Laso3Pablo Ríos-Marco4Antonio Ríos5Daniela Lanari6Archimede Torretta7Emilio Parisini8Luisa C. López-Cara9Carmen Marco10María P. Carrasco-Jiménez11Department of Biochemistry and Molecular Biology I, University of Granada, 18071 Granada, SpainDepartment of Biochemistry and Molecular Biology I, University of Granada, 18071 Granada, SpainDepartment of Pharmaceutical and Organic Chemistry, University of Granada, 18071 Granada, SpainDepartment of Biochemistry and Molecular Biology I, University of Granada, 18071 Granada, SpainDepartment of Biochemistry and Molecular Biology I, University of Granada, 18071 Granada, SpainDepartment of Cell Biology, University of Granada, 18071 Granada, SpainDepartment of Pharmaceutical Sciences, University of Perugia, 06123 Perugia, ItalyCenter for Nano Science and Technology @Polimi, Istituto Italiano di Tecnologia, Via Pascoli 70/3, 20133 Milano, ItalyCenter for Nano Science and Technology @Polimi, Istituto Italiano di Tecnologia, Via Pascoli 70/3, 20133 Milano, ItalyDepartment of Pharmaceutical and Organic Chemistry, University of Granada, 18071 Granada, SpainDepartment of Biochemistry and Molecular Biology I, University of Granada, 18071 Granada, SpainDepartment of Biochemistry and Molecular Biology I, University of Granada, 18071 Granada, SpainA 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 α1 (ChoKα1), the enzyme that catalyses the bioconversion of choline to phosphocholine (PCho), has been found to associate with cell proliferation, oncogenic transformation and carcinogenesis. Hence, ChoKα1 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 ChoKα1, 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 ChoKα1 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 ChoKα1 activity, making both proteins potential targets in cancer therapy.https://www.mdpi.com/1999-4923/14/2/426cancerlipid metabolismcholine kinase inhibitorscholine uptake |
| spellingShingle | Pablo García-Molina Alberto Sola-Leyva Pilar M. Luque-Navarro Alejandro Laso Pablo Ríos-Marco Antonio Ríos Daniela Lanari Archimede Torretta Emilio Parisini Luisa C. López-Cara Carmen Marco María P. Carrasco-Jiménez Anticancer Activity of the Choline Kinase Inhibitor PL48 Is Due to Selective Disruption of Choline Metabolism and Transport Systems in Cancer Cell Lines Pharmaceutics cancer lipid metabolism choline kinase inhibitors 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 |
| title_full | Anticancer Activity of the Choline Kinase Inhibitor PL48 Is Due to Selective Disruption of Choline Metabolism and Transport Systems in Cancer Cell Lines |
| title_fullStr | Anticancer Activity of the Choline Kinase Inhibitor PL48 Is Due to Selective Disruption of Choline Metabolism and Transport Systems in Cancer Cell Lines |
| title_full_unstemmed | Anticancer Activity of the Choline Kinase Inhibitor PL48 Is Due to Selective Disruption of Choline Metabolism and Transport Systems in Cancer Cell Lines |
| title_short | Anticancer Activity of the Choline Kinase Inhibitor PL48 Is Due to Selective Disruption of Choline Metabolism and Transport Systems in Cancer Cell Lines |
| title_sort | anticancer activity of the choline kinase inhibitor pl48 is due to selective disruption of choline metabolism and transport systems in cancer cell lines |
| topic | cancer lipid metabolism choline kinase inhibitors choline uptake |
| url | https://www.mdpi.com/1999-4923/14/2/426 |
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