Investigation of Novel Small Molecular TRPM4 Inhibitors in Colorectal Cancer Cells

(1) Background: Transient receptor potential melastatin (TRPM4) ion channel aberrant expression or malfunction contributes to different types of cancer, including colorectal cancer (CRC). However, TRPM4 still needs to be validated as a potential target in anti-cancer therapy. Currently, the lack of...

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Autores principales:	Paulina Stokłosa, Anna Borgström, Barbara Hauert, Roland Baur, Christine Peinelt
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	TRPM4 ion channels small molecule inhibitors patch clamp Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/c1e2856b9b9d4b049042d1da2ff96539
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spelling	oai:doaj.org-article:c1e2856b9b9d4b049042d1da2ff965392021-11-11T15:30:12ZInvestigation of Novel Small Molecular TRPM4 Inhibitors in Colorectal Cancer Cells10.3390/cancers132154002072-6694https://doaj.org/article/c1e2856b9b9d4b049042d1da2ff965392021-10-01T00:00:00Zhttps://www.mdpi.com/2072-6694/13/21/5400https://doaj.org/toc/2072-6694(1) Background: Transient receptor potential melastatin (TRPM4) ion channel aberrant expression or malfunction contributes to different types of cancer, including colorectal cancer (CRC). However, TRPM4 still needs to be validated as a potential target in anti-cancer therapy. Currently, the lack of potent and selective TRPM4 inhibitors limits further studies on TRPM4 in cancer disease models. In this study, we validated novel TRPM4 inhibitors, CBA, NBA, and LBA, in CRC cells. (2) Methods: The potency to inhibit TRPM4 conductivity in CRC cells was assessed with the whole-cell patch clamp technique. Furthermore, the impact of TRPM4 inhibitors on cellular functions, such as viability, proliferation, and cell cycle, were assessed in cellular assays. (3) Results: We show that in CRC cells, novel TRPM4 inhibitors irreversibly block TRPM4 currents in a low micromolar range. NBA decreases proliferation and alters the cell cycle in HCT116 cells. Furthermore, NBA reduces the viability of the Colo205 cell line, which highly expresses TRPM4. (4) Conclusions: NBA is a promising new TRPM4 inhibitor candidate, which could be used to study the role of TRPM4 in cancer disease models and other diseases.Paulina StokłosaAnna BorgströmBarbara HauertRoland BaurChristine PeineltMDPI AGarticleTRPM4ion channelssmall molecule inhibitorspatch clampNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENCancers, Vol 13, Iss 5400, p 5400 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	TRPM4 ion channels small molecule inhibitors patch clamp Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	TRPM4 ion channels small molecule inhibitors patch clamp Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Paulina Stokłosa Anna Borgström Barbara Hauert Roland Baur Christine Peinelt Investigation of Novel Small Molecular TRPM4 Inhibitors in Colorectal Cancer Cells
description	(1) Background: Transient receptor potential melastatin (TRPM4) ion channel aberrant expression or malfunction contributes to different types of cancer, including colorectal cancer (CRC). However, TRPM4 still needs to be validated as a potential target in anti-cancer therapy. Currently, the lack of potent and selective TRPM4 inhibitors limits further studies on TRPM4 in cancer disease models. In this study, we validated novel TRPM4 inhibitors, CBA, NBA, and LBA, in CRC cells. (2) Methods: The potency to inhibit TRPM4 conductivity in CRC cells was assessed with the whole-cell patch clamp technique. Furthermore, the impact of TRPM4 inhibitors on cellular functions, such as viability, proliferation, and cell cycle, were assessed in cellular assays. (3) Results: We show that in CRC cells, novel TRPM4 inhibitors irreversibly block TRPM4 currents in a low micromolar range. NBA decreases proliferation and alters the cell cycle in HCT116 cells. Furthermore, NBA reduces the viability of the Colo205 cell line, which highly expresses TRPM4. (4) Conclusions: NBA is a promising new TRPM4 inhibitor candidate, which could be used to study the role of TRPM4 in cancer disease models and other diseases.
format	article
author	Paulina Stokłosa Anna Borgström Barbara Hauert Roland Baur Christine Peinelt
author_facet	Paulina Stokłosa Anna Borgström Barbara Hauert Roland Baur Christine Peinelt
author_sort	Paulina Stokłosa
title	Investigation of Novel Small Molecular TRPM4 Inhibitors in Colorectal Cancer Cells
title_short	Investigation of Novel Small Molecular TRPM4 Inhibitors in Colorectal Cancer Cells
title_full	Investigation of Novel Small Molecular TRPM4 Inhibitors in Colorectal Cancer Cells
title_fullStr	Investigation of Novel Small Molecular TRPM4 Inhibitors in Colorectal Cancer Cells
title_full_unstemmed	Investigation of Novel Small Molecular TRPM4 Inhibitors in Colorectal Cancer Cells
title_sort	investigation of novel small molecular trpm4 inhibitors in colorectal cancer cells
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/c1e2856b9b9d4b049042d1da2ff96539
work_keys_str_mv	AT paulinastokłosa investigationofnovelsmallmoleculartrpm4inhibitorsincolorectalcancercells AT annaborgstrom investigationofnovelsmallmoleculartrpm4inhibitorsincolorectalcancercells AT barbarahauert investigationofnovelsmallmoleculartrpm4inhibitorsincolorectalcancercells AT rolandbaur investigationofnovelsmallmoleculartrpm4inhibitorsincolorectalcancercells AT christinepeinelt investigationofnovelsmallmoleculartrpm4inhibitorsincolorectalcancercells
_version_	1718435267097919488

Investigation of Novel Small Molecular TRPM4 Inhibitors in Colorectal Cancer Cells

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