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Analysis of regulating activities of 5′-epiequisetin on proliferation, apoptosis, and migration of prostate cancer cells in vitro and in vivo

Advanced prostate cancer has a poor prognosis, and it is urgent to develop new effective drugs. 5′-Epiequisetin is a tetramic acid derivative which was isolated from a marine sponge-derived fungus Fusarium equiseti in our previous study. In this study, 5′-epiequisetin showed cytotoxicity against fou...

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Autores principales: Wang, Xueni, Luo, Xiaowei, Gan, Xia, Chen, Chunmei, Yang, Zaizhun, Wen, Jing, Fang, Wenxuan, Huang, Hailing, Gao, Chenghai, Zhou, Xuefeng, Feng, Xiaotao, Liu, Yonghong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9399367/
https://www.ncbi.nlm.nih.gov/pubmed/36034825
http://dx.doi.org/10.3389/fphar.2022.920554
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author Wang, Xueni
Luo, Xiaowei
Gan, Xia
Chen, Chunmei
Yang, Zaizhun
Wen, Jing
Fang, Wenxuan
Huang, Hailing
Gao, Chenghai
Zhou, Xuefeng
Feng, Xiaotao
Liu, Yonghong
author_facet Wang, Xueni
Luo, Xiaowei
Gan, Xia
Chen, Chunmei
Yang, Zaizhun
Wen, Jing
Fang, Wenxuan
Huang, Hailing
Gao, Chenghai
Zhou, Xuefeng
Feng, Xiaotao
Liu, Yonghong
author_sort Wang, Xueni
collection PubMed
description Advanced prostate cancer has a poor prognosis, and it is urgent to develop new effective drugs. 5′-Epiequisetin is a tetramic acid derivative which was isolated from a marine sponge-derived fungus Fusarium equiseti in our previous study. In this study, 5′-epiequisetin showed cytotoxicity against four prostate cancer cell lines, namely, LNCaP, 22Rv1, DU145, and PC-3 cells, with the lowest IC(50) value of 4.43 ± 0.24 μM in PC-3 cells. Further studies showed that it could dramatically regulate the clonal colony formation, apoptosis, and migration of PC-3 cells. In addition, flow cytometry data showed that 5′-epiequisetin could block the cell cycle at the G1 phase. Proteome profiler array and Western blot revealed that 5′-epiequisetin could regulate the expression of proteins responsible for cell proliferation, apoptosis, and migration. 5′-Epiequisetin regulated the expression of PI3K, Akt, phosphorylated Akt, and proteins which control the cell cycle. Meanwhile, 5′-epiequisetin upregulated expression of DR5 and cleave-caspase 3, which play important roles in the process of apoptosis. Moreover, when DR5 was silenced by small interfering RNA, the proportion of apoptotic cells induced by 5′-epiequisetin remarkably declined. In addition, 5′-epiequisetin downregulated the expression of survivin which plays a key role in the process of survival and apoptosis. 5′-Epiequisetin also impacted beta-catenin and cadherins, which were associated with cell migration. In addition, 5′-Epiequisetin significantly inhibited the progression of prostate cancer in mice, accompanied by regulating the protein expression of DR5, caspase 8, survivin, and cadherins in vivo. Taken together, these findings indicated that 5′-epiequisetin showed an anti–prostate cancer effect by inducing apoptosis and inhibiting cell proliferation and migration both in vitro and in vivo, suggesting a promising lead compound for the pharmacotherapy of prostate cancer.
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spelling pubmed-93993672022-08-25 Analysis of regulating activities of 5′-epiequisetin on proliferation, apoptosis, and migration of prostate cancer cells in vitro and in vivo Wang, Xueni Luo, Xiaowei Gan, Xia Chen, Chunmei Yang, Zaizhun Wen, Jing Fang, Wenxuan Huang, Hailing Gao, Chenghai Zhou, Xuefeng Feng, Xiaotao Liu, Yonghong Front Pharmacol Pharmacology Advanced prostate cancer has a poor prognosis, and it is urgent to develop new effective drugs. 5′-Epiequisetin is a tetramic acid derivative which was isolated from a marine sponge-derived fungus Fusarium equiseti in our previous study. In this study, 5′-epiequisetin showed cytotoxicity against four prostate cancer cell lines, namely, LNCaP, 22Rv1, DU145, and PC-3 cells, with the lowest IC(50) value of 4.43 ± 0.24 μM in PC-3 cells. Further studies showed that it could dramatically regulate the clonal colony formation, apoptosis, and migration of PC-3 cells. In addition, flow cytometry data showed that 5′-epiequisetin could block the cell cycle at the G1 phase. Proteome profiler array and Western blot revealed that 5′-epiequisetin could regulate the expression of proteins responsible for cell proliferation, apoptosis, and migration. 5′-Epiequisetin regulated the expression of PI3K, Akt, phosphorylated Akt, and proteins which control the cell cycle. Meanwhile, 5′-epiequisetin upregulated expression of DR5 and cleave-caspase 3, which play important roles in the process of apoptosis. Moreover, when DR5 was silenced by small interfering RNA, the proportion of apoptotic cells induced by 5′-epiequisetin remarkably declined. In addition, 5′-epiequisetin downregulated the expression of survivin which plays a key role in the process of survival and apoptosis. 5′-Epiequisetin also impacted beta-catenin and cadherins, which were associated with cell migration. In addition, 5′-Epiequisetin significantly inhibited the progression of prostate cancer in mice, accompanied by regulating the protein expression of DR5, caspase 8, survivin, and cadherins in vivo. Taken together, these findings indicated that 5′-epiequisetin showed an anti–prostate cancer effect by inducing apoptosis and inhibiting cell proliferation and migration both in vitro and in vivo, suggesting a promising lead compound for the pharmacotherapy of prostate cancer. Frontiers Media S.A. 2022-08-10 /pmc/articles/PMC9399367/ /pubmed/36034825 http://dx.doi.org/10.3389/fphar.2022.920554 Text en Copyright © 2022 Wang, Luo, Gan, Chen, Yang, Wen, Fang, Huang, Gao, Zhou, Feng and Liu. 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
Wang, Xueni
Luo, Xiaowei
Gan, Xia
Chen, Chunmei
Yang, Zaizhun
Wen, Jing
Fang, Wenxuan
Huang, Hailing
Gao, Chenghai
Zhou, Xuefeng
Feng, Xiaotao
Liu, Yonghong
Analysis of regulating activities of 5′-epiequisetin on proliferation, apoptosis, and migration of prostate cancer cells in vitro and in vivo
title Analysis of regulating activities of 5′-epiequisetin on proliferation, apoptosis, and migration of prostate cancer cells in vitro and in vivo
title_full Analysis of regulating activities of 5′-epiequisetin on proliferation, apoptosis, and migration of prostate cancer cells in vitro and in vivo
title_fullStr Analysis of regulating activities of 5′-epiequisetin on proliferation, apoptosis, and migration of prostate cancer cells in vitro and in vivo
title_full_unstemmed Analysis of regulating activities of 5′-epiequisetin on proliferation, apoptosis, and migration of prostate cancer cells in vitro and in vivo
title_short Analysis of regulating activities of 5′-epiequisetin on proliferation, apoptosis, and migration of prostate cancer cells in vitro and in vivo
title_sort analysis of regulating activities of 5′-epiequisetin on proliferation, apoptosis, and migration of prostate cancer cells in vitro and in vivo
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9399367/
https://www.ncbi.nlm.nih.gov/pubmed/36034825
http://dx.doi.org/10.3389/fphar.2022.920554
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