Monobenzone, a Novel and Potent KDM1A Inhibitor, Suppresses Migration of Gastric Cancer Cells
Lysine-specific demethylase1 (KDM1A) is generally highly expressed in various cancer tissues, and promotes the initiation and development of cancers via diverse cellular signaling pathways. Therefore, KDM1A is a promising drug target in many cancers, and it is crucial to find effective KDM1A inhibit...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-04-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2021.640949/full |
| _version_ | 1818435534019624960 |
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| author | Peizhi Ma Gang Jia Zhiyu Song |
| author_facet | Peizhi Ma Gang Jia Zhiyu Song |
| author_sort | Peizhi Ma |
| collection | DOAJ |
| description | Lysine-specific demethylase1 (KDM1A) is generally highly expressed in various cancer tissues, and promotes the initiation and development of cancers via diverse cellular signaling pathways. Therefore, KDM1A is a promising drug target in many cancers, and it is crucial to find effective KDM1A inhibitors, while none of them has entered into market. With the help of compound library, monobenzone, a local depigmentor using as a treating over-pigmentation in clinic, was characterized as an effective KDM1A inhibitor (IC50 = 0.4507 μM), which may competitively inhibit KDM1A reversibly. Further cellular study confirmed that monobenzone could inhibit the proliferation of gastric cancer cell lines MGC-803 and BGC-823 with IC50 as 7.82 ± 0.55 μM and 6.99 ± 0.51 μM, respectively, and erase the substrate of KDM1A, H3K4me1/2 and H3K9 me2, and inhibit the migration of gastric cancer cell by reversing epithelial–mesenchymal transition (EMT). As the structure of monobenzone is very simple and small, this study provides a novel backbone for the further optimization of KDM1A inhibitor and gives monobenzone potential new application. |
| first_indexed | 2024-12-14T16:54:24Z |
| format | Article |
| id | doaj.art-59d7d41d3c91466eb61a72ba334fcd49 |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-12-14T16:54:24Z |
| publishDate | 2021-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-59d7d41d3c91466eb61a72ba334fcd492022-12-21T22:54:00ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122021-04-011210.3389/fphar.2021.640949640949Monobenzone, a Novel and Potent KDM1A Inhibitor, Suppresses Migration of Gastric Cancer CellsPeizhi Ma0Gang Jia1Zhiyu Song2Department of Pharmacy, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou, Henan, ChinaDepartment of Oncology, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou, Henan, ChinaDepartment of Pharmacy, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou, Henan, ChinaLysine-specific demethylase1 (KDM1A) is generally highly expressed in various cancer tissues, and promotes the initiation and development of cancers via diverse cellular signaling pathways. Therefore, KDM1A is a promising drug target in many cancers, and it is crucial to find effective KDM1A inhibitors, while none of them has entered into market. With the help of compound library, monobenzone, a local depigmentor using as a treating over-pigmentation in clinic, was characterized as an effective KDM1A inhibitor (IC50 = 0.4507 μM), which may competitively inhibit KDM1A reversibly. Further cellular study confirmed that monobenzone could inhibit the proliferation of gastric cancer cell lines MGC-803 and BGC-823 with IC50 as 7.82 ± 0.55 μM and 6.99 ± 0.51 μM, respectively, and erase the substrate of KDM1A, H3K4me1/2 and H3K9 me2, and inhibit the migration of gastric cancer cell by reversing epithelial–mesenchymal transition (EMT). As the structure of monobenzone is very simple and small, this study provides a novel backbone for the further optimization of KDM1A inhibitor and gives monobenzone potential new application.https://www.frontiersin.org/articles/10.3389/fphar.2021.640949/fullmonobenzoneKDM1A inhibitorgastric cancermigrationEpithelial–mesenchymal transitionH3K4me1/2, H3K9me1/2 |
| spellingShingle | Peizhi Ma Gang Jia Zhiyu Song Monobenzone, a Novel and Potent KDM1A Inhibitor, Suppresses Migration of Gastric Cancer Cells Frontiers in Pharmacology monobenzone KDM1A inhibitor gastric cancer migration Epithelial–mesenchymal transition H3K4me1/2, H3K9me1/2 |
| title | Monobenzone, a Novel and Potent KDM1A Inhibitor, Suppresses Migration of Gastric Cancer Cells |
| title_full | Monobenzone, a Novel and Potent KDM1A Inhibitor, Suppresses Migration of Gastric Cancer Cells |
| title_fullStr | Monobenzone, a Novel and Potent KDM1A Inhibitor, Suppresses Migration of Gastric Cancer Cells |
| title_full_unstemmed | Monobenzone, a Novel and Potent KDM1A Inhibitor, Suppresses Migration of Gastric Cancer Cells |
| title_short | Monobenzone, a Novel and Potent KDM1A Inhibitor, Suppresses Migration of Gastric Cancer Cells |
| title_sort | monobenzone a novel and potent kdm1a inhibitor suppresses migration of gastric cancer cells |
| topic | monobenzone KDM1A inhibitor gastric cancer migration Epithelial–mesenchymal transition H3K4me1/2, H3K9me1/2 |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2021.640949/full |
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