Investigation of Novel Small Molecular TRPM4 Inhibitors in Colorectal Cancer Cells.

Stoklosa, Paulina; Borgström, Anna; Hauert, Barbara; Baur, Roland; Peinelt, Christine (2021). Investigation of Novel Small Molecular TRPM4 Inhibitors in Colorectal Cancer Cells. Cancers, 13(21) MDPI AG 10.3390/cancers13215400

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(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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Biochemistry and Molecular Medicine

UniBE Contributor:

Stoklosa, Paulina Agnieszka, Borgström, Anna, Hauert, Barbara, Baur, Roland, Peinelt, Christine

Subjects:

500 Science > 570 Life sciences; biology
600 Technology > 610 Medicine & health

ISSN:

2072-6694

Publisher:

MDPI AG

Language:

English

Submitter:

Barbara Franziska Järmann-Bangerter

Date Deposited:

30 Nov 2021 09:08

Last Modified:

05 Dec 2022 15:55

Publisher DOI:

10.3390/cancers13215400

PubMed ID:

34771564

Uncontrolled Keywords:

TRPM4 ion channels patch clamp small molecule inhibitors

BORIS DOI:

10.48350/161543

URI:

https://boris.unibe.ch/id/eprint/161543

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