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ANO1-downregulation induced by schisandrathera D: a novel therapeutic target for the treatment of prostate and oral cancers
Anoctamin 1 (ANO1), a drug target for various cancers, including prostate and oral cancers, is an intracellular calcium-activated chloride ion channel that plays various physiopathological roles, especially in the induction of cancer growth and metastasis. In this study, we tested a novel compound i...
Autores principales: | , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10232832/ https://www.ncbi.nlm.nih.gov/pubmed/37274097 http://dx.doi.org/10.3389/fphar.2023.1163970 |
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author | Park, SeonJu Das, Raju Nhiem, Nguyen Xuan Jeong, Sung Baek Kim, Minuk Kim, Dongguk Oh, Hye In Cho, Su-Hyeon Kwon, Oh-Bin Choi, Jae-Hyeog Park, Chul Soon Kim, Song-Rae Moon, Uk Yeol Cha, Boksik Choi, Dong Kyu Lee, Sungwoo Namkung, Wan Woo, Joohan Seo, Yohan |
author_facet | Park, SeonJu Das, Raju Nhiem, Nguyen Xuan Jeong, Sung Baek Kim, Minuk Kim, Dongguk Oh, Hye In Cho, Su-Hyeon Kwon, Oh-Bin Choi, Jae-Hyeog Park, Chul Soon Kim, Song-Rae Moon, Uk Yeol Cha, Boksik Choi, Dong Kyu Lee, Sungwoo Namkung, Wan Woo, Joohan Seo, Yohan |
author_sort | Park, SeonJu |
collection | PubMed |
description | Anoctamin 1 (ANO1), a drug target for various cancers, including prostate and oral cancers, is an intracellular calcium-activated chloride ion channel that plays various physiopathological roles, especially in the induction of cancer growth and metastasis. In this study, we tested a novel compound isolated from Schisandra sphenanthera, known as schisandrathera D, for its inhibitory effect on ANO1. Schisandrathera D dose-dependently suppressed the ANO1 activation-mediated decrease in fluorescence of yellow fluorescent protein; however, it did not affect the adenosine triphosphate-induced increase in the intracellular calcium concentration or forskolin-induced cystic fibrosis transmembrane conductance regulator activity. Specifically, schisandrathera D gradually decreased the levels of ANO1 protein and significantly reduced the cell viability in ANO1-expressing cells when compared to those in ANO1-knockout cells. These effects could be attributed to the fact that schisandrathera D displayed better binding capacity to ANO1 protein than the previously known ANO1 inhibitor, Ani9. Finally, schisandrathera D increased the levels of caspase-3 and cleaved poly (ADP-ribose) polymerase 1, thereby indicating that its anticancer effect is mediated through apoptosis. Thus, this study highlights that schisandrathera D, which reduces ANO1 protein levels, has apoptosis-mediated anticancer effects in prostate and oral cancers, and thus, can be further developed into an anticancer agent. |
format | Online Article Text |
id | pubmed-10232832 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-102328322023-06-02 ANO1-downregulation induced by schisandrathera D: a novel therapeutic target for the treatment of prostate and oral cancers Park, SeonJu Das, Raju Nhiem, Nguyen Xuan Jeong, Sung Baek Kim, Minuk Kim, Dongguk Oh, Hye In Cho, Su-Hyeon Kwon, Oh-Bin Choi, Jae-Hyeog Park, Chul Soon Kim, Song-Rae Moon, Uk Yeol Cha, Boksik Choi, Dong Kyu Lee, Sungwoo Namkung, Wan Woo, Joohan Seo, Yohan Front Pharmacol Pharmacology Anoctamin 1 (ANO1), a drug target for various cancers, including prostate and oral cancers, is an intracellular calcium-activated chloride ion channel that plays various physiopathological roles, especially in the induction of cancer growth and metastasis. In this study, we tested a novel compound isolated from Schisandra sphenanthera, known as schisandrathera D, for its inhibitory effect on ANO1. Schisandrathera D dose-dependently suppressed the ANO1 activation-mediated decrease in fluorescence of yellow fluorescent protein; however, it did not affect the adenosine triphosphate-induced increase in the intracellular calcium concentration or forskolin-induced cystic fibrosis transmembrane conductance regulator activity. Specifically, schisandrathera D gradually decreased the levels of ANO1 protein and significantly reduced the cell viability in ANO1-expressing cells when compared to those in ANO1-knockout cells. These effects could be attributed to the fact that schisandrathera D displayed better binding capacity to ANO1 protein than the previously known ANO1 inhibitor, Ani9. Finally, schisandrathera D increased the levels of caspase-3 and cleaved poly (ADP-ribose) polymerase 1, thereby indicating that its anticancer effect is mediated through apoptosis. Thus, this study highlights that schisandrathera D, which reduces ANO1 protein levels, has apoptosis-mediated anticancer effects in prostate and oral cancers, and thus, can be further developed into an anticancer agent. Frontiers Media S.A. 2023-05-18 /pmc/articles/PMC10232832/ /pubmed/37274097 http://dx.doi.org/10.3389/fphar.2023.1163970 Text en Copyright © 2023 Park, Das, Nhiem, Jeong, Kim, Kim, Oh, Cho, Kwon, Choi, Park, Kim, Moon, Cha, Choi, Lee, Namkung, Woo and Seo. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Pharmacology Park, SeonJu Das, Raju Nhiem, Nguyen Xuan Jeong, Sung Baek Kim, Minuk Kim, Dongguk Oh, Hye In Cho, Su-Hyeon Kwon, Oh-Bin Choi, Jae-Hyeog Park, Chul Soon Kim, Song-Rae Moon, Uk Yeol Cha, Boksik Choi, Dong Kyu Lee, Sungwoo Namkung, Wan Woo, Joohan Seo, Yohan ANO1-downregulation induced by schisandrathera D: a novel therapeutic target for the treatment of prostate and oral cancers |
title | ANO1-downregulation induced by schisandrathera D: a novel therapeutic target for the treatment of prostate and oral cancers |
title_full | ANO1-downregulation induced by schisandrathera D: a novel therapeutic target for the treatment of prostate and oral cancers |
title_fullStr | ANO1-downregulation induced by schisandrathera D: a novel therapeutic target for the treatment of prostate and oral cancers |
title_full_unstemmed | ANO1-downregulation induced by schisandrathera D: a novel therapeutic target for the treatment of prostate and oral cancers |
title_short | ANO1-downregulation induced by schisandrathera D: a novel therapeutic target for the treatment of prostate and oral cancers |
title_sort | ano1-downregulation induced by schisandrathera d: a novel therapeutic target for the treatment of prostate and oral cancers |
topic | Pharmacology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10232832/ https://www.ncbi.nlm.nih.gov/pubmed/37274097 http://dx.doi.org/10.3389/fphar.2023.1163970 |
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