CBA (4-chloro-2-(2-chlorophenoxy)acetamido) benzoic acid) inhibits TMEM206 mediated currents and TMEM206 does not contribute to acid-induced cell death in colorectal cancer cells
Introduction: Upon activation at low pH, TMEM206 conducts Cl− ions across plasma and vesicular membranes. In a (patho)physiological context, TMEM206 was reported to contribute to acid-induced cell death in neurons, kidney and cervical epithelial cells. We investigated the role of TMEM206 in acid-ind...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2024-03-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2024.1369513/full |
| _version_ | 1797271103524044800 |
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| author | Sven Kappel Korollus Melek Daniela Ross-Kaschitza Barbara Hauert Christian E. Gerber Martin Lochner Christine Peinelt |
| author_facet | Sven Kappel Korollus Melek Daniela Ross-Kaschitza Barbara Hauert Christian E. Gerber Martin Lochner Christine Peinelt |
| author_sort | Sven Kappel |
| collection | DOAJ |
| description | Introduction: Upon activation at low pH, TMEM206 conducts Cl− ions across plasma and vesicular membranes. In a (patho)physiological context, TMEM206 was reported to contribute to acid-induced cell death in neurons, kidney and cervical epithelial cells. We investigated the role of TMEM206 in acid-induced cell death in colorectal cancer cells. In addition, we studied CBA as a new small molecule inhibitor for TMEM206.Methods: The role of TMEM206 in acid-induced cell death was studied with CRISPR/Cas9-mediated knockout and FACS analysis. The pharmacology of TMEM206 was determined with the patch clamp technique.Results: In colorectal cancer cells, TMEM206 is not a critical mediator of acid-induced cell death. CBA is a small molecule inhibitor of TMEM206 (IC50 = 9.55 µM) at low pH, at pH 6.0 inhibition is limited.Conclusion: CBA demonstrates effective and specific inhibition of TMEM206; however, its inhibitory efficacy is limited at pH 6.0. Despite this limitation, CBA is a potent inhibitor for functional studies at pH 4.5 and may be a promising scaffold for the development of future TMEM206 inhibitors. |
| first_indexed | 2024-04-25T02:14:51Z |
| format | Article |
| id | doaj.art-503c6247f68848779b4f4a3c5e221059 |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-04-25T02:14:51Z |
| publishDate | 2024-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-503c6247f68848779b4f4a3c5e2210592024-03-07T10:07:48ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122024-03-011510.3389/fphar.2024.13695131369513CBA (4-chloro-2-(2-chlorophenoxy)acetamido) benzoic acid) inhibits TMEM206 mediated currents and TMEM206 does not contribute to acid-induced cell death in colorectal cancer cellsSven KappelKorollus MelekDaniela Ross-KaschitzaBarbara HauertChristian E. GerberMartin LochnerChristine PeineltIntroduction: Upon activation at low pH, TMEM206 conducts Cl− ions across plasma and vesicular membranes. In a (patho)physiological context, TMEM206 was reported to contribute to acid-induced cell death in neurons, kidney and cervical epithelial cells. We investigated the role of TMEM206 in acid-induced cell death in colorectal cancer cells. In addition, we studied CBA as a new small molecule inhibitor for TMEM206.Methods: The role of TMEM206 in acid-induced cell death was studied with CRISPR/Cas9-mediated knockout and FACS analysis. The pharmacology of TMEM206 was determined with the patch clamp technique.Results: In colorectal cancer cells, TMEM206 is not a critical mediator of acid-induced cell death. CBA is a small molecule inhibitor of TMEM206 (IC50 = 9.55 µM) at low pH, at pH 6.0 inhibition is limited.Conclusion: CBA demonstrates effective and specific inhibition of TMEM206; however, its inhibitory efficacy is limited at pH 6.0. Despite this limitation, CBA is a potent inhibitor for functional studies at pH 4.5 and may be a promising scaffold for the development of future TMEM206 inhibitors.https://www.frontiersin.org/articles/10.3389/fphar.2024.1369513/fullTMEM206PAORACASORsmall molecule inhibitorcolorectal cancer |
| spellingShingle | Sven Kappel Korollus Melek Daniela Ross-Kaschitza Barbara Hauert Christian E. Gerber Martin Lochner Christine Peinelt CBA (4-chloro-2-(2-chlorophenoxy)acetamido) benzoic acid) inhibits TMEM206 mediated currents and TMEM206 does not contribute to acid-induced cell death in colorectal cancer cells Frontiers in Pharmacology TMEM206 PAORAC ASOR small molecule inhibitor colorectal cancer |
| title | CBA (4-chloro-2-(2-chlorophenoxy)acetamido) benzoic acid) inhibits TMEM206 mediated currents and TMEM206 does not contribute to acid-induced cell death in colorectal cancer cells |
| title_full | CBA (4-chloro-2-(2-chlorophenoxy)acetamido) benzoic acid) inhibits TMEM206 mediated currents and TMEM206 does not contribute to acid-induced cell death in colorectal cancer cells |
| title_fullStr | CBA (4-chloro-2-(2-chlorophenoxy)acetamido) benzoic acid) inhibits TMEM206 mediated currents and TMEM206 does not contribute to acid-induced cell death in colorectal cancer cells |
| title_full_unstemmed | CBA (4-chloro-2-(2-chlorophenoxy)acetamido) benzoic acid) inhibits TMEM206 mediated currents and TMEM206 does not contribute to acid-induced cell death in colorectal cancer cells |
| title_short | CBA (4-chloro-2-(2-chlorophenoxy)acetamido) benzoic acid) inhibits TMEM206 mediated currents and TMEM206 does not contribute to acid-induced cell death in colorectal cancer cells |
| title_sort | cba 4 chloro 2 2 chlorophenoxy acetamido benzoic acid inhibits tmem206 mediated currents and tmem206 does not contribute to acid induced cell death in colorectal cancer cells |
| topic | TMEM206 PAORAC ASOR small molecule inhibitor colorectal cancer |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2024.1369513/full |
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