PCC0208057 as a small molecule inhibitor of TRPC6 in the treatment of prostate cancer
Prostate cancer (PCa) is a common malignant tumor, whose morbidity and mortality keep the top three in the male-related tumors in developed countries. Abnormal ion channels, such as transient receptor potential canonical 6 (TRPC6), are reported to be involved in the carcinogenesis and progress of pr...
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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.2024.1352373/full |
| _version_ | 1827315499524947968 |
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| author | Yingjie Wei Min Li Yuemiao Hu Jing Lu Lin Wang Qikun Yin Xuechuan Hong Jingwei Tian Hongbo Wang |
| author_facet | Yingjie Wei Min Li Yuemiao Hu Jing Lu Lin Wang Qikun Yin Xuechuan Hong Jingwei Tian Hongbo Wang |
| author_sort | Yingjie Wei |
| collection | DOAJ |
| description | Prostate cancer (PCa) is a common malignant tumor, whose morbidity and mortality keep the top three in the male-related tumors in developed countries. Abnormal ion channels, such as transient receptor potential canonical 6 (TRPC6), are reported to be involved in the carcinogenesis and progress of prostate cancer and have become potential drug targets against prostate cancer. Here, we report a novel small molecule inhibitor of TRPC6, designated as PCC0208057, which can suppress the proliferation and migration of prostate cancer cells in vitro, and inhibit the formation of Human umbilical vein endothelial cells cell lumen. PCC0208057 can effectively inhibit the growth of xenograft tumor in vivo. Molecular mechanism studies revealed that PCC0208057 could directly bind and inhibit the activity of TRPC6, which then induces the prostate cancer cells arrested in G2/M phase via enhancing the phosphorylation of Nuclear Factor of Activated T Cells (NFAT) and Cdc2. Taken together, our study describes for the first time that PCC0208057, a novel TRPC6 inhibitor, might be a promising lead compound for treatment of prostate cancer. |
| first_indexed | 2024-04-24T22:56:21Z |
| format | Article |
| id | doaj.art-bc89a953661b480fb6e9679e7d3361fb |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-04-24T22:56:21Z |
| publishDate | 2024-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-bc89a953661b480fb6e9679e7d3361fb2024-03-18T04:48:59ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122024-03-011510.3389/fphar.2024.13523731352373PCC0208057 as a small molecule inhibitor of TRPC6 in the treatment of prostate cancerYingjie Wei0Min Li1Yuemiao Hu2Jing Lu3Lin Wang4Qikun Yin5Xuechuan Hong6Jingwei Tian7Hongbo Wang8School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai, ChinaSchool of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai, ChinaSchool of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai, ChinaSchool of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai, ChinaSchool of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai, ChinaSchool of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai, ChinaKey Laboratory of Combinatorial Biosynthesis and Drug Discovery (MOE) and Hubei Province Engineering and Technology Research Center for Fluorinated Pharmaceuticals, Wuhan University School of Pharmaceutical Sciences, Wuhan, ChinaSchool of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai, ChinaSchool of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai, ChinaProstate cancer (PCa) is a common malignant tumor, whose morbidity and mortality keep the top three in the male-related tumors in developed countries. Abnormal ion channels, such as transient receptor potential canonical 6 (TRPC6), are reported to be involved in the carcinogenesis and progress of prostate cancer and have become potential drug targets against prostate cancer. Here, we report a novel small molecule inhibitor of TRPC6, designated as PCC0208057, which can suppress the proliferation and migration of prostate cancer cells in vitro, and inhibit the formation of Human umbilical vein endothelial cells cell lumen. PCC0208057 can effectively inhibit the growth of xenograft tumor in vivo. Molecular mechanism studies revealed that PCC0208057 could directly bind and inhibit the activity of TRPC6, which then induces the prostate cancer cells arrested in G2/M phase via enhancing the phosphorylation of Nuclear Factor of Activated T Cells (NFAT) and Cdc2. Taken together, our study describes for the first time that PCC0208057, a novel TRPC6 inhibitor, might be a promising lead compound for treatment of prostate cancer.https://www.frontiersin.org/articles/10.3389/fphar.2024.1352373/fullprostate cancerTRPC6 channelTRPC6 small molecule inhibitorcycle arrestgrowth inhibition |
| spellingShingle | Yingjie Wei Min Li Yuemiao Hu Jing Lu Lin Wang Qikun Yin Xuechuan Hong Jingwei Tian Hongbo Wang PCC0208057 as a small molecule inhibitor of TRPC6 in the treatment of prostate cancer Frontiers in Pharmacology prostate cancer TRPC6 channel TRPC6 small molecule inhibitor cycle arrest growth inhibition |
| title | PCC0208057 as a small molecule inhibitor of TRPC6 in the treatment of prostate cancer |
| title_full | PCC0208057 as a small molecule inhibitor of TRPC6 in the treatment of prostate cancer |
| title_fullStr | PCC0208057 as a small molecule inhibitor of TRPC6 in the treatment of prostate cancer |
| title_full_unstemmed | PCC0208057 as a small molecule inhibitor of TRPC6 in the treatment of prostate cancer |
| title_short | PCC0208057 as a small molecule inhibitor of TRPC6 in the treatment of prostate cancer |
| title_sort | pcc0208057 as a small molecule inhibitor of trpc6 in the treatment of prostate cancer |
| topic | prostate cancer TRPC6 channel TRPC6 small molecule inhibitor cycle arrest growth inhibition |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2024.1352373/full |
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