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Hedgehog pathway is involved in nitidine chloride induced inhibition of epithelial-mesenchymal transition and cancer stem cells-like properties in breast cancer cells

BACKGROUND: The complications of clinical metastatic disease are responsible for the majority of breast cancer related deaths, and fewer therapies substantially prolong survival. Nitidine chloride (NC), a natural polyphenolic compound, has been shown to exhibit potent anticancer effects in many canc...

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Autores principales: Sun, Mingjuan, Zhang, Ning, Wang, Xiaolong, Li, Yaming, Qi, Wenwen, Zhang, Hanwen, Li, Zengjun, Yang, Qifeng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4910241/
https://www.ncbi.nlm.nih.gov/pubmed/27313840
http://dx.doi.org/10.1186/s13578-016-0104-8
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author Sun, Mingjuan
Zhang, Ning
Wang, Xiaolong
Li, Yaming
Qi, Wenwen
Zhang, Hanwen
Li, Zengjun
Yang, Qifeng
author_facet Sun, Mingjuan
Zhang, Ning
Wang, Xiaolong
Li, Yaming
Qi, Wenwen
Zhang, Hanwen
Li, Zengjun
Yang, Qifeng
author_sort Sun, Mingjuan
collection PubMed
description BACKGROUND: The complications of clinical metastatic disease are responsible for the majority of breast cancer related deaths, and fewer therapies substantially prolong survival. Nitidine chloride (NC), a natural polyphenolic compound, has been shown to exhibit potent anticancer effects in many cancer types, including breast cancer. The epithelial-mesenchymal transition (EMT) and the acquisition of cancer stem cells (CSCs)-like properties emerge as critical steps in the metastasis of human cancers. However, the effects of NC on the EMT and the CSCs-like properties in breast cancer cells, and the underlying molecular mechanisms are not fully understood. RESULTS: In the present study, MDA-MB-468 and MCF-7 cancer cells were treated with NC. Scratch and Transwell assays were performed to determine whether NC could attenuate the migratory and invasive capability of cancer cells; Mammosphere formation and flow cytometry analysis were performed to confirm that NC decreased CSCs-like phenotype; RT-PCR and western blot analysis were used to examine the expression level of EMT and CSC related markers in both cells. Mechanistically, NC could inhibit the components of Hedgehog pathway (smoothened, patched, Gli1 and Gli2), subsequently inhibited the expression of Snail, Slug and Zeb1, which were correlated with the significant changes of the expression of EMT related markers (N-cadherin, E-cadherin, and Vimentin) to reverse EMT. On the other hand, NC could also inhibit the expression of CSCs related factors such as Nanog, Nestin, Oct-4 and CD44 via Hedgehog pathway. Furthermore, transforming growth factor-β1 (TGF-β1)-induced increment of EMT and CSCs properties could be reversed by NC. CONCLUSIONS: Taken together, these data indicated that NC suppressed breast cancer EMT and CSCs-like properties through inhibiting Hedgehog signaling pathway. Our study suggested that NC may be a potential anticancer agent for breast cancer.
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spelling pubmed-49102412016-06-17 Hedgehog pathway is involved in nitidine chloride induced inhibition of epithelial-mesenchymal transition and cancer stem cells-like properties in breast cancer cells Sun, Mingjuan Zhang, Ning Wang, Xiaolong Li, Yaming Qi, Wenwen Zhang, Hanwen Li, Zengjun Yang, Qifeng Cell Biosci Research BACKGROUND: The complications of clinical metastatic disease are responsible for the majority of breast cancer related deaths, and fewer therapies substantially prolong survival. Nitidine chloride (NC), a natural polyphenolic compound, has been shown to exhibit potent anticancer effects in many cancer types, including breast cancer. The epithelial-mesenchymal transition (EMT) and the acquisition of cancer stem cells (CSCs)-like properties emerge as critical steps in the metastasis of human cancers. However, the effects of NC on the EMT and the CSCs-like properties in breast cancer cells, and the underlying molecular mechanisms are not fully understood. RESULTS: In the present study, MDA-MB-468 and MCF-7 cancer cells were treated with NC. Scratch and Transwell assays were performed to determine whether NC could attenuate the migratory and invasive capability of cancer cells; Mammosphere formation and flow cytometry analysis were performed to confirm that NC decreased CSCs-like phenotype; RT-PCR and western blot analysis were used to examine the expression level of EMT and CSC related markers in both cells. Mechanistically, NC could inhibit the components of Hedgehog pathway (smoothened, patched, Gli1 and Gli2), subsequently inhibited the expression of Snail, Slug and Zeb1, which were correlated with the significant changes of the expression of EMT related markers (N-cadherin, E-cadherin, and Vimentin) to reverse EMT. On the other hand, NC could also inhibit the expression of CSCs related factors such as Nanog, Nestin, Oct-4 and CD44 via Hedgehog pathway. Furthermore, transforming growth factor-β1 (TGF-β1)-induced increment of EMT and CSCs properties could be reversed by NC. CONCLUSIONS: Taken together, these data indicated that NC suppressed breast cancer EMT and CSCs-like properties through inhibiting Hedgehog signaling pathway. Our study suggested that NC may be a potential anticancer agent for breast cancer. BioMed Central 2016-06-16 /pmc/articles/PMC4910241/ /pubmed/27313840 http://dx.doi.org/10.1186/s13578-016-0104-8 Text en © The Author(s) 2016 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Sun, Mingjuan
Zhang, Ning
Wang, Xiaolong
Li, Yaming
Qi, Wenwen
Zhang, Hanwen
Li, Zengjun
Yang, Qifeng
Hedgehog pathway is involved in nitidine chloride induced inhibition of epithelial-mesenchymal transition and cancer stem cells-like properties in breast cancer cells
title Hedgehog pathway is involved in nitidine chloride induced inhibition of epithelial-mesenchymal transition and cancer stem cells-like properties in breast cancer cells
title_full Hedgehog pathway is involved in nitidine chloride induced inhibition of epithelial-mesenchymal transition and cancer stem cells-like properties in breast cancer cells
title_fullStr Hedgehog pathway is involved in nitidine chloride induced inhibition of epithelial-mesenchymal transition and cancer stem cells-like properties in breast cancer cells
title_full_unstemmed Hedgehog pathway is involved in nitidine chloride induced inhibition of epithelial-mesenchymal transition and cancer stem cells-like properties in breast cancer cells
title_short Hedgehog pathway is involved in nitidine chloride induced inhibition of epithelial-mesenchymal transition and cancer stem cells-like properties in breast cancer cells
title_sort hedgehog pathway is involved in nitidine chloride induced inhibition of epithelial-mesenchymal transition and cancer stem cells-like properties in breast cancer cells
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4910241/
https://www.ncbi.nlm.nih.gov/pubmed/27313840
http://dx.doi.org/10.1186/s13578-016-0104-8
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