Penfluridol targets septin7 to suppress endometrial cancer by septin7-Orai/IP3R-Ca2+-PIK3CA pathway
Summary: Phenotypic screening of existing drugs is a good strategy to discover new drugs. Herein, 33 psychotherapeutic drugs in our drug library were screened by phenotypic screening and penfluridol (PFD) was found to exhibit excellent anti-endometrial cancer (EC) activity both in vitro and in vivo....
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| Format: | Article |
| Language: | English |
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Elsevier
2025-01-01
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| Series: | iScience |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004224028670 |
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| author | Lingyi Song Huiwen Wu Xiao Sun Xiaohu Liu Xianwu Ling Wei Ni Lijuan Li Beibei Liu Jinlian Wei Xiaokang Li Jian Li Yudong Wang Fei Mao |
| author_facet | Lingyi Song Huiwen Wu Xiao Sun Xiaohu Liu Xianwu Ling Wei Ni Lijuan Li Beibei Liu Jinlian Wei Xiaokang Li Jian Li Yudong Wang Fei Mao |
| author_sort | Lingyi Song |
| collection | DOAJ |
| description | Summary: Phenotypic screening of existing drugs is a good strategy to discover new drugs. Herein, 33 psychotherapeutic drugs in our drug library were screened by phenotypic screening and penfluridol (PFD) was found to exhibit excellent anti-endometrial cancer (EC) activity both in vitro and in vivo. Furthermore, the molecular target of PFD was identified as septin7, a tumor suppressor in EC. In septin7-deficient EC cells and xenograft mouse models, PFD exhibited weaker anti-cancer properties, indicating that septin7 was essential for the tumor inhibitory activity. Notably, PFD could induce cell apoptosis by regulating the septin7-Orai/IP3R-Ca2+-PIK3CA pathway. In addition, PFD attenuates the interaction of septin7-tubulin, thereby inhibiting microtubule polymerization. In summary, this study revealed a target and mechanistic insights into EC therapeutic strategies and identified a potential candidate agent for the treatment of EC. |
| format | Article |
| id | doaj-art-930b8a0ddb6344b28e9a36f8b03f9e5b |
| institution | Kabale University |
| issn | 2589-0042 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj-art-930b8a0ddb6344b28e9a36f8b03f9e5b2025-01-04T04:56:49ZengElsevieriScience2589-00422025-01-01281111640Penfluridol targets septin7 to suppress endometrial cancer by septin7-Orai/IP3R-Ca2+-PIK3CA pathwayLingyi Song0Huiwen Wu1Xiao Sun2Xiaohu Liu3Xianwu Ling4Wei Ni5Lijuan Li6Beibei Liu7Jinlian Wei8Xiaokang Li9Jian Li10Yudong Wang11Fei Mao12State Key Laboratory of Bioreactor Engineering, Shanghai Frontiers Science Center of Optogenetic Techniques for Cell Metabolism, Frontiers Science Center for Materiobiology and Dynamic Chemistry, Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, ChinaState Key Laboratory of Bioreactor Engineering, Shanghai Frontiers Science Center of Optogenetic Techniques for Cell Metabolism, Frontiers Science Center for Materiobiology and Dynamic Chemistry, Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, ChinaDepartment of Gynecologic Oncology, the International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, ChinaState Key Laboratory of Bioreactor Engineering, Shanghai Frontiers Science Center of Optogenetic Techniques for Cell Metabolism, Frontiers Science Center for Materiobiology and Dynamic Chemistry, Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, ChinaState Key Laboratory of Bioreactor Engineering, Shanghai Frontiers Science Center of Optogenetic Techniques for Cell Metabolism, Frontiers Science Center for Materiobiology and Dynamic Chemistry, Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, ChinaState Key Laboratory of Bioreactor Engineering, Shanghai Frontiers Science Center of Optogenetic Techniques for Cell Metabolism, Frontiers Science Center for Materiobiology and Dynamic Chemistry, Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, ChinaDepartment of Gynecologic Oncology, the International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, ChinaState Key Laboratory of Bioreactor Engineering, Shanghai Frontiers Science Center of Optogenetic Techniques for Cell Metabolism, Frontiers Science Center for Materiobiology and Dynamic Chemistry, Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, ChinaState Key Laboratory of Bioreactor Engineering, Shanghai Frontiers Science Center of Optogenetic Techniques for Cell Metabolism, Frontiers Science Center for Materiobiology and Dynamic Chemistry, Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, ChinaState Key Laboratory of Bioreactor Engineering, Shanghai Frontiers Science Center of Optogenetic Techniques for Cell Metabolism, Frontiers Science Center for Materiobiology and Dynamic Chemistry, Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, ChinaState Key Laboratory of Bioreactor Engineering, Shanghai Frontiers Science Center of Optogenetic Techniques for Cell Metabolism, Frontiers Science Center for Materiobiology and Dynamic Chemistry, Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China; Key Laboratory of Xinjiang Phytomedicine Resource and Utilization, Ministry of Education, School of Pharmacy, Shihezi University, Shihezi 832003, China; Key Laboratory of Tropical Biological Resources of Ministry of Education, College of Pharmacy, Hainan University, Haikou 570228, China; Corresponding authorDepartment of Gynecologic Oncology, the International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, China; Shanghai Municipal Key Clinical Specialty, Female Tumor Reproductive Specialty, Shanghai 200030, China; Corresponding authorState Key Laboratory of Bioreactor Engineering, Shanghai Frontiers Science Center of Optogenetic Techniques for Cell Metabolism, Frontiers Science Center for Materiobiology and Dynamic Chemistry, Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China; Corresponding authorSummary: Phenotypic screening of existing drugs is a good strategy to discover new drugs. Herein, 33 psychotherapeutic drugs in our drug library were screened by phenotypic screening and penfluridol (PFD) was found to exhibit excellent anti-endometrial cancer (EC) activity both in vitro and in vivo. Furthermore, the molecular target of PFD was identified as septin7, a tumor suppressor in EC. In septin7-deficient EC cells and xenograft mouse models, PFD exhibited weaker anti-cancer properties, indicating that septin7 was essential for the tumor inhibitory activity. Notably, PFD could induce cell apoptosis by regulating the septin7-Orai/IP3R-Ca2+-PIK3CA pathway. In addition, PFD attenuates the interaction of septin7-tubulin, thereby inhibiting microtubule polymerization. In summary, this study revealed a target and mechanistic insights into EC therapeutic strategies and identified a potential candidate agent for the treatment of EC.http://www.sciencedirect.com/science/article/pii/S2589004224028670Cell biologyFunctional aspects of cell biologyCancer |
| spellingShingle | Lingyi Song Huiwen Wu Xiao Sun Xiaohu Liu Xianwu Ling Wei Ni Lijuan Li Beibei Liu Jinlian Wei Xiaokang Li Jian Li Yudong Wang Fei Mao Penfluridol targets septin7 to suppress endometrial cancer by septin7-Orai/IP3R-Ca2+-PIK3CA pathway iScience Cell biology Functional aspects of cell biology Cancer |
| title | Penfluridol targets septin7 to suppress endometrial cancer by septin7-Orai/IP3R-Ca2+-PIK3CA pathway |
| title_full | Penfluridol targets septin7 to suppress endometrial cancer by septin7-Orai/IP3R-Ca2+-PIK3CA pathway |
| title_fullStr | Penfluridol targets septin7 to suppress endometrial cancer by septin7-Orai/IP3R-Ca2+-PIK3CA pathway |
| title_full_unstemmed | Penfluridol targets septin7 to suppress endometrial cancer by septin7-Orai/IP3R-Ca2+-PIK3CA pathway |
| title_short | Penfluridol targets septin7 to suppress endometrial cancer by septin7-Orai/IP3R-Ca2+-PIK3CA pathway |
| title_sort | penfluridol targets septin7 to suppress endometrial cancer by septin7 orai ip3r ca2 pik3ca pathway |
| topic | Cell biology Functional aspects of cell biology Cancer |
| url | http://www.sciencedirect.com/science/article/pii/S2589004224028670 |
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