The anti-tumor drug 2-hydroxyoleic acid regulates the oncogenic potassium channel Kv10.1
Abstract Background 2-hydroxyoleic acid (2OHOA) is a synthetic fatty acid with antitumor properties that alters membrane composition and structure, which in turn influences the functioning of membrane proteins and cell signaling. In this study, we propose a novel antitumoral mechanism of 2OHOA accom...
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| Format: | Article |
| Language: | English |
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SpringerOpen
2023-02-01
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| Series: | Beni-Suef University Journal of Basic and Applied Sciences |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s43088-023-00354-z |
| _version_ | 1828041538967437312 |
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| author | Rita Morán-Zendejas Aldo A. Rodríguez-Menchaca |
| author_facet | Rita Morán-Zendejas Aldo A. Rodríguez-Menchaca |
| author_sort | Rita Morán-Zendejas |
| collection | DOAJ |
| description | Abstract Background 2-hydroxyoleic acid (2OHOA) is a synthetic fatty acid with antitumor properties that alters membrane composition and structure, which in turn influences the functioning of membrane proteins and cell signaling. In this study, we propose a novel antitumoral mechanism of 2OHOA accomplished through the regulation of Kv10.1 channels. We evaluated the effects of 2OHOA on Kv10.1 channels expressed in HEK-293 cells by using electrophysiological techniques and a cell proliferation assay. Results 2OHOA increased Kv10.1 channel currents in a voltage-dependent manner, shifted its conductance-voltage relationship towards negative potentials, and accelerated its activation kinetics. Moreover, 2OHOA reduced proliferation of cells that exogenously (HEK-293) and endogenously (MCF-7) expressed Kv10.1 channels. It is worth noting that the antiproliferative effect of 2OHOA was maintained in HEK-293 cells expressing a non-conducting mutant of Kv10.1 channel (Kv10.1-F456A), while it did not affect HEK-293 cells not expressing Kv10.1 channels, suggesting that 2OHOA interferes with a non-conducting function of Kv10.1 channels involved in cell proliferation. Finally, we found that 2OHOA can act synergistically with astemizole, a Kv10.1 channel blocker, to decrease cell proliferation more efficiently. Conclusion Our data suggest that 2OHOA decreases cell proliferation, at least in part, by regulating Kv10.1 channels. |
| first_indexed | 2024-04-10T17:17:45Z |
| format | Article |
| id | doaj.art-e23fd1fc8f59434d813cae059013c69f |
| institution | Directory Open Access Journal |
| issn | 2314-8543 |
| language | English |
| last_indexed | 2024-04-10T17:17:45Z |
| publishDate | 2023-02-01 |
| publisher | SpringerOpen |
| record_format | Article |
| series | Beni-Suef University Journal of Basic and Applied Sciences |
| spelling | doaj.art-e23fd1fc8f59434d813cae059013c69f2023-02-05T12:20:40ZengSpringerOpenBeni-Suef University Journal of Basic and Applied Sciences2314-85432023-02-011211810.1186/s43088-023-00354-zThe anti-tumor drug 2-hydroxyoleic acid regulates the oncogenic potassium channel Kv10.1Rita Morán-Zendejas0Aldo A. Rodríguez-Menchaca1Departamento de Fisiología y Biofísica, Facultad de Medicina, Universidad Autónoma de San Luis PotosíDepartamento de Fisiología y Biofísica, Facultad de Medicina, Universidad Autónoma de San Luis PotosíAbstract Background 2-hydroxyoleic acid (2OHOA) is a synthetic fatty acid with antitumor properties that alters membrane composition and structure, which in turn influences the functioning of membrane proteins and cell signaling. In this study, we propose a novel antitumoral mechanism of 2OHOA accomplished through the regulation of Kv10.1 channels. We evaluated the effects of 2OHOA on Kv10.1 channels expressed in HEK-293 cells by using electrophysiological techniques and a cell proliferation assay. Results 2OHOA increased Kv10.1 channel currents in a voltage-dependent manner, shifted its conductance-voltage relationship towards negative potentials, and accelerated its activation kinetics. Moreover, 2OHOA reduced proliferation of cells that exogenously (HEK-293) and endogenously (MCF-7) expressed Kv10.1 channels. It is worth noting that the antiproliferative effect of 2OHOA was maintained in HEK-293 cells expressing a non-conducting mutant of Kv10.1 channel (Kv10.1-F456A), while it did not affect HEK-293 cells not expressing Kv10.1 channels, suggesting that 2OHOA interferes with a non-conducting function of Kv10.1 channels involved in cell proliferation. Finally, we found that 2OHOA can act synergistically with astemizole, a Kv10.1 channel blocker, to decrease cell proliferation more efficiently. Conclusion Our data suggest that 2OHOA decreases cell proliferation, at least in part, by regulating Kv10.1 channels.https://doi.org/10.1186/s43088-023-00354-zPotassium channelsSynthetic lipidsElectrophysiologyCell proliferation |
| spellingShingle | Rita Morán-Zendejas Aldo A. Rodríguez-Menchaca The anti-tumor drug 2-hydroxyoleic acid regulates the oncogenic potassium channel Kv10.1 Beni-Suef University Journal of Basic and Applied Sciences Potassium channels Synthetic lipids Electrophysiology Cell proliferation |
| title | The anti-tumor drug 2-hydroxyoleic acid regulates the oncogenic potassium channel Kv10.1 |
| title_full | The anti-tumor drug 2-hydroxyoleic acid regulates the oncogenic potassium channel Kv10.1 |
| title_fullStr | The anti-tumor drug 2-hydroxyoleic acid regulates the oncogenic potassium channel Kv10.1 |
| title_full_unstemmed | The anti-tumor drug 2-hydroxyoleic acid regulates the oncogenic potassium channel Kv10.1 |
| title_short | The anti-tumor drug 2-hydroxyoleic acid regulates the oncogenic potassium channel Kv10.1 |
| title_sort | anti tumor drug 2 hydroxyoleic acid regulates the oncogenic potassium channel kv10 1 |
| topic | Potassium channels Synthetic lipids Electrophysiology Cell proliferation |
| url | https://doi.org/10.1186/s43088-023-00354-z |
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