Guanine inhibits the growth of human glioma and melanoma cell lines by interacting with GPR23
Guanine-based purines (GBPs) exert numerous biological effects at the central nervous system through putative membrane receptors, the existence of which is still elusive. To shed light on this question, we screened orphan and poorly characterized G protein-coupled receptors (GPRs), selecting those t...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-09-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2022.970891/full |
| _version_ | 1811266989438533632 |
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| author | Roberta Garozzo Mariachiara Zuccarini Mariachiara Zuccarini Patricia Giuliani Patricia Giuliani Valentina Di Liberto Giuseppa Mudò Francesco Caciagli Renata Ciccarelli Francisco Ciruela Francisco Ciruela Patrizia Di Iorio Patrizia Di Iorio Daniele F. Condorelli |
| author_facet | Roberta Garozzo Mariachiara Zuccarini Mariachiara Zuccarini Patricia Giuliani Patricia Giuliani Valentina Di Liberto Giuseppa Mudò Francesco Caciagli Renata Ciccarelli Francisco Ciruela Francisco Ciruela Patrizia Di Iorio Patrizia Di Iorio Daniele F. Condorelli |
| author_sort | Roberta Garozzo |
| collection | DOAJ |
| description | Guanine-based purines (GBPs) exert numerous biological effects at the central nervous system through putative membrane receptors, the existence of which is still elusive. To shed light on this question, we screened orphan and poorly characterized G protein-coupled receptors (GPRs), selecting those that showed a high purinoreceptor similarity and were expressed in glioma cells, where GBPs exerted a powerful antiproliferative effect. Of the GPRs chosen, only the silencing of GPR23, also known as lysophosphatidic acid (LPA) 4 receptor, counteracted GBP-induced growth inhibition in U87 cells. Guanine (GUA) was the most potent compound behind the GPR23-mediated effect, acting as the endpoint effector of GBP antiproliferative effects. Accordingly, cells stably expressing GPR23 showed increased sensitivity to GUA. Furthermore, while GPR23 expression was low in a hypoxanthine-guanine phosphoribosyl-transferase (HGPRT)-mutated melanoma cell line showing poor sensitivity to GBPs, and in HGPRT-silenced glioma cells, GPR23-induced expression in both cell types rescued GUA-mediated cell growth inhibition. Finally, binding experiments using [3H]-GUA and U87 cell membranes revealed the existence of a selective GUA binding (KD = 29.44 ± 4.07 nM; Bmax 1.007 ± 0.035 pmol/mg prot) likely to GPR23. Overall, these data suggest GPR23 involvement in modulating responses to GUA in tumor cell lines, although further research needs to verify whether this receptor mediates other GUA effects. |
| first_indexed | 2024-04-12T20:53:18Z |
| format | Article |
| id | doaj.art-21d16f6458fc4a458234e5702031a48b |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-04-12T20:53:18Z |
| publishDate | 2022-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-21d16f6458fc4a458234e5702031a48b2022-12-22T03:17:03ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122022-09-011310.3389/fphar.2022.970891970891Guanine inhibits the growth of human glioma and melanoma cell lines by interacting with GPR23Roberta Garozzo0Mariachiara Zuccarini1Mariachiara Zuccarini2Patricia Giuliani3Patricia Giuliani4Valentina Di Liberto5Giuseppa Mudò6Francesco Caciagli7Renata Ciccarelli8Francisco Ciruela9Francisco Ciruela10Patrizia Di Iorio11Patrizia Di Iorio12Daniele F. Condorelli13Department of Biomedical and Biotechnological, Section of Medical Biochemistry, University of Catania, Catania, ItalyDepartment of Medical, Oral and Biotechnological Sciences, Section of Pharmacology and Toxicology, School of Medicine, University of Chieti-Pescara, Chieti, ItalyCenter for Advanced Studies and Technologies (CAST), University of Chieti-Pescara, Chieti, ItalyDepartment of Medical, Oral and Biotechnological Sciences, Section of Pharmacology and Toxicology, School of Medicine, University of Chieti-Pescara, Chieti, ItalyCenter for Advanced Studies and Technologies (CAST), University of Chieti-Pescara, Chieti, ItalyDepartment of Biomedicine, Neuroscience and Advanced Diagnostic, University of Palermo, Palermo, ItalyDepartment of Biomedicine, Neuroscience and Advanced Diagnostic, University of Palermo, Palermo, ItalyCenter for Advanced Studies and Technologies (CAST), University of Chieti-Pescara, Chieti, ItalyCenter for Advanced Studies and Technologies (CAST), University of Chieti-Pescara, Chieti, ItalyPharmacology Unit, Department of Pathology and Experimental Therapeutics, Faculty of Medicine and Health Sciences, Institute of Neurosciences, University of Barcelona, Barcelona, SpainNeuropharmacology and Pain Group, Neuroscience Program, Institut d’Investigació Biomèdica de Bellvitge, IDIBELL, Barcelona, SpainDepartment of Medical, Oral and Biotechnological Sciences, Section of Pharmacology and Toxicology, School of Medicine, University of Chieti-Pescara, Chieti, ItalyCenter for Advanced Studies and Technologies (CAST), University of Chieti-Pescara, Chieti, ItalyDepartment of Biomedical and Biotechnological, Section of Medical Biochemistry, University of Catania, Catania, ItalyGuanine-based purines (GBPs) exert numerous biological effects at the central nervous system through putative membrane receptors, the existence of which is still elusive. To shed light on this question, we screened orphan and poorly characterized G protein-coupled receptors (GPRs), selecting those that showed a high purinoreceptor similarity and were expressed in glioma cells, where GBPs exerted a powerful antiproliferative effect. Of the GPRs chosen, only the silencing of GPR23, also known as lysophosphatidic acid (LPA) 4 receptor, counteracted GBP-induced growth inhibition in U87 cells. Guanine (GUA) was the most potent compound behind the GPR23-mediated effect, acting as the endpoint effector of GBP antiproliferative effects. Accordingly, cells stably expressing GPR23 showed increased sensitivity to GUA. Furthermore, while GPR23 expression was low in a hypoxanthine-guanine phosphoribosyl-transferase (HGPRT)-mutated melanoma cell line showing poor sensitivity to GBPs, and in HGPRT-silenced glioma cells, GPR23-induced expression in both cell types rescued GUA-mediated cell growth inhibition. Finally, binding experiments using [3H]-GUA and U87 cell membranes revealed the existence of a selective GUA binding (KD = 29.44 ± 4.07 nM; Bmax 1.007 ± 0.035 pmol/mg prot) likely to GPR23. Overall, these data suggest GPR23 involvement in modulating responses to GUA in tumor cell lines, although further research needs to verify whether this receptor mediates other GUA effects.https://www.frontiersin.org/articles/10.3389/fphar.2022.970891/fullguanine-based purines (GBPs)guanine (GUA)purine nucleoside phosphorylase (PNP)antiproliferative effectsG protein-coupled receptor 23 (GPR23)glioma cell lines |
| spellingShingle | Roberta Garozzo Mariachiara Zuccarini Mariachiara Zuccarini Patricia Giuliani Patricia Giuliani Valentina Di Liberto Giuseppa Mudò Francesco Caciagli Renata Ciccarelli Francisco Ciruela Francisco Ciruela Patrizia Di Iorio Patrizia Di Iorio Daniele F. Condorelli Guanine inhibits the growth of human glioma and melanoma cell lines by interacting with GPR23 Frontiers in Pharmacology guanine-based purines (GBPs) guanine (GUA) purine nucleoside phosphorylase (PNP) antiproliferative effects G protein-coupled receptor 23 (GPR23) glioma cell lines |
| title | Guanine inhibits the growth of human glioma and melanoma cell lines by interacting with GPR23 |
| title_full | Guanine inhibits the growth of human glioma and melanoma cell lines by interacting with GPR23 |
| title_fullStr | Guanine inhibits the growth of human glioma and melanoma cell lines by interacting with GPR23 |
| title_full_unstemmed | Guanine inhibits the growth of human glioma and melanoma cell lines by interacting with GPR23 |
| title_short | Guanine inhibits the growth of human glioma and melanoma cell lines by interacting with GPR23 |
| title_sort | guanine inhibits the growth of human glioma and melanoma cell lines by interacting with gpr23 |
| topic | guanine-based purines (GBPs) guanine (GUA) purine nucleoside phosphorylase (PNP) antiproliferative effects G protein-coupled receptor 23 (GPR23) glioma cell lines |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2022.970891/full |
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