Cimigenoside functions as a novel γ-secretase inhibitor and inhibits the proliferation or metastasis of human breast cancer cells by γ-secretase/Notch axis
Breast cancer (BC) occurrence and development tremendously affect female health. Currently breast cancer targeted drugs are still scarce. Natural products have become the main source of targeted drug for breast cancer due to low toxicity and high efficiency. Cimigenoside, natural compound isolated a...
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Published in | Pharmacological research Vol. 169; p. 105686 |
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Main Authors | , , , , , , , , |
Format | Journal Article |
Language | English |
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Elsevier Ltd
01.07.2021
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Abstract | Breast cancer (BC) occurrence and development tremendously affect female health. Currently breast cancer targeted drugs are still scarce. Natural products have become the main source of targeted drug for breast cancer due to low toxicity and high efficiency. Cimigenoside, natural compound isolated and purified from Cimicifuga dahurica (Turcz.) Maxim has been suggested to utilize for breast cancer treatment, however the mechanism of action has not been elucidated yet. In this article, the antitumor potential of Cimigenoside against breast cancer in vitro and in vivo study. Moreover, we further predicted the possible binding mode of Cimigenoside with γ-secretase through molecular docking studies. The results show that Cimigenoside has a significant inhibitory effect towards the proliferation or metastasis of breast cancer cells via suppressing the Notch signaling pathway-mediated mitochondrial apoptosis and EMT (epithelial mesenchymal transition). In terms of mechanism, Cimigenoside could inhibit the activation of PSEN-1, the catalytic subunit of γ-secretase, and also by cleaving the Notch protein mediated by PSEN-1. Overall, our findings provide scientific support to utilize Cimigenoside as an effective targeted drug for clinical treatment of BC.
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●Cimigenoside inhibits the growth of human breast cancer in vivo and in vitro.●Cimigenoside exerts anti-tumor activity by blocking Notch signaling pathway.●Cimigenoside inhibits the activation of the catalytic subunit PSEN-1 of γ-secretase.●Cimigenoside is expected to become a potential therapeutic drug for breast cancer. |
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AbstractList | Breast cancer (BC) occurrence and development tremendously affect female health. Currently breast cancer targeted drugs are still scarce. Natural products have become the main source of targeted drug for breast cancer due to low toxicity and high efficiency. Cimigenoside, natural compound isolated and purified from Cimicifuga dahurica (Turcz.) Maxim has been suggested to utilize for breast cancer treatment, however the mechanism of action has not been elucidated yet. In this article, the antitumor potential of Cimigenoside against breast cancer in vitro and in vivo study. Moreover, we further predicted the possible binding mode of Cimigenoside with γ-secretase through molecular docking studies. The results show that Cimigenoside has a significant inhibitory effect towards the proliferation or metastasis of breast cancer cells via suppressing the Notch signaling pathway-mediated mitochondrial apoptosis and EMT (epithelial mesenchymal transition). In terms of mechanism, Cimigenoside could inhibit the activation of PSEN-1, the catalytic subunit of γ-secretase, and also by cleaving the Notch protein mediated by PSEN-1. Overall, our findings provide scientific support to utilize Cimigenoside as an effective targeted drug for clinical treatment of BC. Breast cancer (BC) occurrence and development tremendously affect female health. Currently breast cancer targeted drugs are still scarce. Natural products have become the main source of targeted drug for breast cancer due to low toxicity and high efficiency. Cimigenoside, natural compound isolated and purified from Cimicifuga dahurica (Turcz.) Maxim has been suggested to utilize for breast cancer treatment, however the mechanism of action has not been elucidated yet. In this article, the antitumor potential of Cimigenoside against breast cancer in vitro and in vivo study. Moreover, we further predicted the possible binding mode of Cimigenoside with γ-secretase through molecular docking studies. The results show that Cimigenoside has a significant inhibitory effect towards the proliferation or metastasis of breast cancer cells via suppressing the Notch signaling pathway-mediated mitochondrial apoptosis and EMT (epithelial mesenchymal transition). In terms of mechanism, Cimigenoside could inhibit the activation of PSEN-1, the catalytic subunit of γ-secretase, and also by cleaving the Notch protein mediated by PSEN-1. Overall, our findings provide scientific support to utilize Cimigenoside as an effective targeted drug for clinical treatment of BC. [Display omitted] ●Cimigenoside inhibits the growth of human breast cancer in vivo and in vitro.●Cimigenoside exerts anti-tumor activity by blocking Notch signaling pathway.●Cimigenoside inhibits the activation of the catalytic subunit PSEN-1 of γ-secretase.●Cimigenoside is expected to become a potential therapeutic drug for breast cancer. |
ArticleNumber | 105686 |
Author | Santhanam, Ramesh Kumar Jia, Hui Liu, Mingyue Wang, Xinying Lu, Jincai Jiang, Qiyu Wang, Shu Lv, Chongning Zhao, Qingchun |
Author_xml | – sequence: 1 givenname: Hui surname: Jia fullname: Jia, Hui email: smockingandy@163.com organization: School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110006, PR China – sequence: 2 givenname: Mingyue surname: Liu fullname: Liu, Mingyue email: liumingyue18@163.com organization: Department of Life Science and Biochemistry, Shenyang Pharmaceutical University, Shenyang 110016, PR China – sequence: 3 givenname: Xinying surname: Wang fullname: Wang, Xinying email: wxyspu@126.com organization: School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110006, PR China – sequence: 4 givenname: Qiyu surname: Jiang fullname: Jiang, Qiyu email: jiangqy1991@sina.com organization: Center for Clinical Laboratory, The Fifth Medical Center, General Hospital of Chinese PLA, Beijing 100039, PR China – sequence: 5 givenname: Shu surname: Wang fullname: Wang, Shu email: wangshu521@163.com organization: Department of Life Science and Biochemistry, Shenyang Pharmaceutical University, Shenyang 110016, PR China – sequence: 6 givenname: Ramesh Kumar surname: Santhanam fullname: Santhanam, Ramesh Kumar email: ramesh@umt.edu.my organization: Faculty of Science and Marine Environment, Universiti Malaysia Terengganu, Kuala Nerus 21030, Terengganu, Malaysia – sequence: 7 givenname: Chongning surname: Lv fullname: Lv, Chongning email: lcnmi@outlook.com organization: School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110006, PR China – sequence: 8 givenname: Qingchun surname: Zhao fullname: Zhao, Qingchun email: zhaoqingchun1967@163.com organization: Department of Life Science and Biochemistry, Shenyang Pharmaceutical University, Shenyang 110016, PR China – sequence: 9 givenname: Jincai surname: Lu fullname: Lu, Jincai email: jincailu@syphu.edu.cn organization: School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110006, PR China |
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Keywords | Breast cancer γ-secretase PSEN-1 EMT Notch Apoptosis |
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Snippet | Breast cancer (BC) occurrence and development tremendously affect female health. Currently breast cancer targeted drugs are still scarce. Natural products have... |
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SubjectTerms | Amyloid Precursor Protein Secretases - antagonists & inhibitors Amyloid Precursor Protein Secretases - metabolism Animals Antineoplastic Agents - pharmacology Antineoplastic Agents - therapeutic use Apoptosis Breast cancer Breast Neoplasms - drug therapy Cell Line, Tumor - drug effects Cell Proliferation - drug effects EMT Female Humans MCF-7 Cells - drug effects Membrane Potential, Mitochondrial - drug effects Mice Mice, Inbred BALB C Mice, Nude Molecular Docking Simulation Neoplasm Transplantation Notch PSEN-1 Receptors, Notch - metabolism Triterpenes - pharmacology Triterpenes - therapeutic use γ-secretase |
Title | Cimigenoside functions as a novel γ-secretase inhibitor and inhibits the proliferation or metastasis of human breast cancer cells by γ-secretase/Notch axis |
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