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Anti-tumor Effect of Rhaponticum uniflorum Ethyl Acetate Extract by Regulation of Peroxiredoxin1 and Epithelial-to-Mesenchymal Transition in Oral Cancer

Objective: To explore whether Rhaponticum uniflorum (R. uniflorum) had anti-tumor effects in oral cancer and investigate the molecular mechanisms involved in these anti-tumor effects. Methods: Chemical compositions of R. uniflorum ethyl acetate (RUEA) extracts were detected by ultra-performance liqu...

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Autores principales: Chen, Hui, Wang, Chunxiao, Qi, Moci, Ge, Lihua, Tian, Zhenchuan, Li, Jinhua, Zhang, Min, Wang, Min, Huang, Linfang, Tang, Xiaofei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5703707/
https://www.ncbi.nlm.nih.gov/pubmed/29218012
http://dx.doi.org/10.3389/fphar.2017.00870
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author Chen, Hui
Wang, Chunxiao
Qi, Moci
Ge, Lihua
Tian, Zhenchuan
Li, Jinhua
Zhang, Min
Wang, Min
Huang, Linfang
Tang, Xiaofei
author_facet Chen, Hui
Wang, Chunxiao
Qi, Moci
Ge, Lihua
Tian, Zhenchuan
Li, Jinhua
Zhang, Min
Wang, Min
Huang, Linfang
Tang, Xiaofei
author_sort Chen, Hui
collection PubMed
description Objective: To explore whether Rhaponticum uniflorum (R. uniflorum) had anti-tumor effects in oral cancer and investigate the molecular mechanisms involved in these anti-tumor effects. Methods: Chemical compositions of R. uniflorum ethyl acetate (RUEA) extracts were detected by ultra-performance liquid chromatography-Q/time-of-flight mass spectrometry (UPLC-Q/TOF-MS), followed by pharmacology-based network prediction analysis. The effects of RUEA extracts on proliferation, apoptosis, migration, and invasion ability of human oral squamous cell carcinoma (OSCC) cell line SCC15 were evaluated by CCK8 assay, Annexin V- fluorescein isothiocyanate/propidium iodide staining, wound healing assay, and Matrigel invasion assay, respectively. The mRNA and protein expression of peroxiredoxin1 (Prx1), the epithelial-to-mesenchymal transition (EMT) marker E-cadherin, vimentin, and Snail were determined by quantitative real-time reverse transcription polymerase chain reaction and western blotting. A mouse xenograft model of SCC15 cells was established to further evaluate the effect of RUEA extracts in vivo. Immunohistochemical assessment of Ki67 and terminal deoxynucleotidyl transferase dUTP nick end labeling staining of apoptotic cells were performed on the tumor tissues to assess the effects of RUEA extracts on proliferation and apoptosis. Results: Fourteen compounds were identified from RUEA extracts by UPLC-Q/TOF-MS. The pharmacology-based network prediction analysis showed that Prx1 could be a potential binder of RUEA extracts. In SCC15 cells, RUEA extracts inhibited cell viability, induced apoptosis, and suppressed cell invasion and migration in a concentration-dependent manner. After treatment with RUEA extracts, the mRNA and protein expression of E-cadherin increased, whereas those of Prx1, vimentin, and Snail decreased. RUEA extracts also affected the EMT program and suppressed cell invasion and migration in Prx1 knockdown SCC15 cells. In an OSCC mouse xenograft model, RUEA extracts (25 and 250 mg/kg) significantly inhibited the growth of tumors. Compared with the control group, Ki67 expression was reduced and apoptosis rates were elevated in the transplanted tumors treated with RUEA extracts. RUEA extracts increased the expression of E-cadherin and decreased the expression of Prx1, vimentin, and Snail in vivo. Conclusion: RUEA extracts inhibited tumor growth and invasion by reducing Prx1 expression and suppressing the EMT process in OSCC. RUEA extracts may be a potential candidate for OSCC treatment.
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spelling pubmed-57037072017-12-07 Anti-tumor Effect of Rhaponticum uniflorum Ethyl Acetate Extract by Regulation of Peroxiredoxin1 and Epithelial-to-Mesenchymal Transition in Oral Cancer Chen, Hui Wang, Chunxiao Qi, Moci Ge, Lihua Tian, Zhenchuan Li, Jinhua Zhang, Min Wang, Min Huang, Linfang Tang, Xiaofei Front Pharmacol Pharmacology Objective: To explore whether Rhaponticum uniflorum (R. uniflorum) had anti-tumor effects in oral cancer and investigate the molecular mechanisms involved in these anti-tumor effects. Methods: Chemical compositions of R. uniflorum ethyl acetate (RUEA) extracts were detected by ultra-performance liquid chromatography-Q/time-of-flight mass spectrometry (UPLC-Q/TOF-MS), followed by pharmacology-based network prediction analysis. The effects of RUEA extracts on proliferation, apoptosis, migration, and invasion ability of human oral squamous cell carcinoma (OSCC) cell line SCC15 were evaluated by CCK8 assay, Annexin V- fluorescein isothiocyanate/propidium iodide staining, wound healing assay, and Matrigel invasion assay, respectively. The mRNA and protein expression of peroxiredoxin1 (Prx1), the epithelial-to-mesenchymal transition (EMT) marker E-cadherin, vimentin, and Snail were determined by quantitative real-time reverse transcription polymerase chain reaction and western blotting. A mouse xenograft model of SCC15 cells was established to further evaluate the effect of RUEA extracts in vivo. Immunohistochemical assessment of Ki67 and terminal deoxynucleotidyl transferase dUTP nick end labeling staining of apoptotic cells were performed on the tumor tissues to assess the effects of RUEA extracts on proliferation and apoptosis. Results: Fourteen compounds were identified from RUEA extracts by UPLC-Q/TOF-MS. The pharmacology-based network prediction analysis showed that Prx1 could be a potential binder of RUEA extracts. In SCC15 cells, RUEA extracts inhibited cell viability, induced apoptosis, and suppressed cell invasion and migration in a concentration-dependent manner. After treatment with RUEA extracts, the mRNA and protein expression of E-cadherin increased, whereas those of Prx1, vimentin, and Snail decreased. RUEA extracts also affected the EMT program and suppressed cell invasion and migration in Prx1 knockdown SCC15 cells. In an OSCC mouse xenograft model, RUEA extracts (25 and 250 mg/kg) significantly inhibited the growth of tumors. Compared with the control group, Ki67 expression was reduced and apoptosis rates were elevated in the transplanted tumors treated with RUEA extracts. RUEA extracts increased the expression of E-cadherin and decreased the expression of Prx1, vimentin, and Snail in vivo. Conclusion: RUEA extracts inhibited tumor growth and invasion by reducing Prx1 expression and suppressing the EMT process in OSCC. RUEA extracts may be a potential candidate for OSCC treatment. Frontiers Media S.A. 2017-11-23 /pmc/articles/PMC5703707/ /pubmed/29218012 http://dx.doi.org/10.3389/fphar.2017.00870 Text en Copyright © 2017 Chen, Wang, Qi, Ge, Tian, Li, Zhang, Wang, Huang and Tang. 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) or licensor 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
Chen, Hui
Wang, Chunxiao
Qi, Moci
Ge, Lihua
Tian, Zhenchuan
Li, Jinhua
Zhang, Min
Wang, Min
Huang, Linfang
Tang, Xiaofei
Anti-tumor Effect of Rhaponticum uniflorum Ethyl Acetate Extract by Regulation of Peroxiredoxin1 and Epithelial-to-Mesenchymal Transition in Oral Cancer
title Anti-tumor Effect of Rhaponticum uniflorum Ethyl Acetate Extract by Regulation of Peroxiredoxin1 and Epithelial-to-Mesenchymal Transition in Oral Cancer
title_full Anti-tumor Effect of Rhaponticum uniflorum Ethyl Acetate Extract by Regulation of Peroxiredoxin1 and Epithelial-to-Mesenchymal Transition in Oral Cancer
title_fullStr Anti-tumor Effect of Rhaponticum uniflorum Ethyl Acetate Extract by Regulation of Peroxiredoxin1 and Epithelial-to-Mesenchymal Transition in Oral Cancer
title_full_unstemmed Anti-tumor Effect of Rhaponticum uniflorum Ethyl Acetate Extract by Regulation of Peroxiredoxin1 and Epithelial-to-Mesenchymal Transition in Oral Cancer
title_short Anti-tumor Effect of Rhaponticum uniflorum Ethyl Acetate Extract by Regulation of Peroxiredoxin1 and Epithelial-to-Mesenchymal Transition in Oral Cancer
title_sort anti-tumor effect of rhaponticum uniflorum ethyl acetate extract by regulation of peroxiredoxin1 and epithelial-to-mesenchymal transition in oral cancer
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5703707/
https://www.ncbi.nlm.nih.gov/pubmed/29218012
http://dx.doi.org/10.3389/fphar.2017.00870
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