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Toxicarioside O Inhibits Cell Proliferation and Epithelial-Mesenchymal Transition by Downregulation of Trop2 in Lung Cancer Cells

Toxicarioside O (TCO), a natural product derived from Antiaris toxicaria, has been identified to be a promising anticancer agent. In this study, we aimed to investigate the effect of TCO on the proliferation and epithelial-mesenchymal transition (EMT) of lung cancer cells and its molecular mechanism...

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Autores principales: Zheng, Wu-Ping, Huang, Feng-Ying, Dai, Shu-Zhen, Wang, Jin-Yan, Lin, Ying-Ying, Sun, Yan, Tan, Guang-Hong, Huang, Yong-Hao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7891104/
https://www.ncbi.nlm.nih.gov/pubmed/33614493
http://dx.doi.org/10.3389/fonc.2020.609275
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author Zheng, Wu-Ping
Huang, Feng-Ying
Dai, Shu-Zhen
Wang, Jin-Yan
Lin, Ying-Ying
Sun, Yan
Tan, Guang-Hong
Huang, Yong-Hao
author_facet Zheng, Wu-Ping
Huang, Feng-Ying
Dai, Shu-Zhen
Wang, Jin-Yan
Lin, Ying-Ying
Sun, Yan
Tan, Guang-Hong
Huang, Yong-Hao
author_sort Zheng, Wu-Ping
collection PubMed
description Toxicarioside O (TCO), a natural product derived from Antiaris toxicaria, has been identified to be a promising anticancer agent. In this study, we aimed to investigate the effect of TCO on the proliferation and epithelial-mesenchymal transition (EMT) of lung cancer cells and its molecular mechanisms. Here, we indicated that TCO inhibits the proliferation of lung cancer cells both in vitro and in vivo. Our results demonstrated that TCO induces apoptosis in lung cancer cells. Moreover, we found that TCO suppresses EMT program and inhibits cell migration in vitro. Mechanistically, TCO decreases the expression of trophoblast cell surface antigen 2 (Trop2), resulting in inhibition of the PI3K/Akt pathway and EMT program. Overexpression of Trop2 rescues TCO-induced inhibition of cell proliferation and EMT. Our findings demonstrate that TCO markedly inhibits cell proliferation and EMT in lung cancer cells and provides guidance for its drug development.
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spelling pubmed-78911042021-02-19 Toxicarioside O Inhibits Cell Proliferation and Epithelial-Mesenchymal Transition by Downregulation of Trop2 in Lung Cancer Cells Zheng, Wu-Ping Huang, Feng-Ying Dai, Shu-Zhen Wang, Jin-Yan Lin, Ying-Ying Sun, Yan Tan, Guang-Hong Huang, Yong-Hao Front Oncol Oncology Toxicarioside O (TCO), a natural product derived from Antiaris toxicaria, has been identified to be a promising anticancer agent. In this study, we aimed to investigate the effect of TCO on the proliferation and epithelial-mesenchymal transition (EMT) of lung cancer cells and its molecular mechanisms. Here, we indicated that TCO inhibits the proliferation of lung cancer cells both in vitro and in vivo. Our results demonstrated that TCO induces apoptosis in lung cancer cells. Moreover, we found that TCO suppresses EMT program and inhibits cell migration in vitro. Mechanistically, TCO decreases the expression of trophoblast cell surface antigen 2 (Trop2), resulting in inhibition of the PI3K/Akt pathway and EMT program. Overexpression of Trop2 rescues TCO-induced inhibition of cell proliferation and EMT. Our findings demonstrate that TCO markedly inhibits cell proliferation and EMT in lung cancer cells and provides guidance for its drug development. Frontiers Media S.A. 2021-02-04 /pmc/articles/PMC7891104/ /pubmed/33614493 http://dx.doi.org/10.3389/fonc.2020.609275 Text en Copyright © 2021 Zheng, Huang, Dai, Wang, Lin, Sun, Tan and Huang http://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 Oncology
Zheng, Wu-Ping
Huang, Feng-Ying
Dai, Shu-Zhen
Wang, Jin-Yan
Lin, Ying-Ying
Sun, Yan
Tan, Guang-Hong
Huang, Yong-Hao
Toxicarioside O Inhibits Cell Proliferation and Epithelial-Mesenchymal Transition by Downregulation of Trop2 in Lung Cancer Cells
title Toxicarioside O Inhibits Cell Proliferation and Epithelial-Mesenchymal Transition by Downregulation of Trop2 in Lung Cancer Cells
title_full Toxicarioside O Inhibits Cell Proliferation and Epithelial-Mesenchymal Transition by Downregulation of Trop2 in Lung Cancer Cells
title_fullStr Toxicarioside O Inhibits Cell Proliferation and Epithelial-Mesenchymal Transition by Downregulation of Trop2 in Lung Cancer Cells
title_full_unstemmed Toxicarioside O Inhibits Cell Proliferation and Epithelial-Mesenchymal Transition by Downregulation of Trop2 in Lung Cancer Cells
title_short Toxicarioside O Inhibits Cell Proliferation and Epithelial-Mesenchymal Transition by Downregulation of Trop2 in Lung Cancer Cells
title_sort toxicarioside o inhibits cell proliferation and epithelial-mesenchymal transition by downregulation of trop2 in lung cancer cells
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7891104/
https://www.ncbi.nlm.nih.gov/pubmed/33614493
http://dx.doi.org/10.3389/fonc.2020.609275
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