Cargando…

Evodiamine Exerts Anticancer Effects Against 143B and MG63 Cells Through the Wnt/β-Catenin Signaling Pathway

BACKGROUND: Osteosarcoma is the most common primary malignant bone neoplasm and is associated with abysmal prognosis. There are limitations of current treatment methods. Therefore, developing new agents to treat osteosarcoma is exceptionally urgent. AIM: This study aimed to evaluate the anticancer e...

Descripción completa

Detalles Bibliográficos
Autores principales: Yang, Shengdong, Chen, Jin, Tan, Tao, Wang, Nan, Huang, Yanran, Wang, Yuping, Yuan, Xiaohui, Zhang, Ping, Luo, Jinyong, Luo, Xiaoji
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7196244/
https://www.ncbi.nlm.nih.gov/pubmed/32425601
http://dx.doi.org/10.2147/CMAR.S238093
_version_ 1783528685689634816
author Yang, Shengdong
Chen, Jin
Tan, Tao
Wang, Nan
Huang, Yanran
Wang, Yuping
Yuan, Xiaohui
Zhang, Ping
Luo, Jinyong
Luo, Xiaoji
author_facet Yang, Shengdong
Chen, Jin
Tan, Tao
Wang, Nan
Huang, Yanran
Wang, Yuping
Yuan, Xiaohui
Zhang, Ping
Luo, Jinyong
Luo, Xiaoji
author_sort Yang, Shengdong
collection PubMed
description BACKGROUND: Osteosarcoma is the most common primary malignant bone neoplasm and is associated with abysmal prognosis. There are limitations of current treatment methods. Therefore, developing new agents to treat osteosarcoma is exceptionally urgent. AIM: This study aimed to evaluate the anticancer effects of evodiamine (EVO) on osteosarcoma cells and, meanwhile, to investigate the underlying mechanisms involved. MATERIALS AND METHODS: The effect of EVO on the proliferation of osteosarcoma was detected by MTT assay, crystal violet assay and colony formation assay. The effects of EVO on the migration and invasion of osteosarcoma were detected by wound-healing assay and transwell assay. The effect of EVO on apoptosis of osteosarcoma was measured by Hoechst 33258 staining and cell cycle assay. The protein expression levels were detected by Western blotting assay. The activity of Wnt/β-Catenin signaling pathway was detected by luciferase reporter assay and Western blotting assay. RESULTS: According to MTT, crystal violet and colony formation assay results, EVO significantly inhibited the cell proliferation in a dose-dependent manner. Hoechst 33258 staining assay revealed that EVO induced cell apoptosis in a concentration-dependent manner. Moreover, EVO inhibited the migration and invasion of the osteosarcoma cells. Mechanistic studies revealed that EVO suppresses metastatic through suppressing epithelial–mesenchymal transition (EMT) as indicated by elevating the expression of epithelial marker E‐cadherin and reducing the expression of mesenchymal markers N‐cadherin and vimentin, as well as EMT transcription factors Snail and MMPs. Subsequently, EVO induced cell cycle arrest at the G2/M phase that correlated with reduced levels of cyclin D1 protein, while the apoptotic effects of EVO were associated with the upregulation of Bax and Bad and a decrease in Bcl-2 protein levels. Furthermore, EVO exerted the anticancer effects by suppressing Wnt/β-catenin signal pathway in osteosarcoma cells. CONCLUSION: In summary, EVO exhibited potent anticancer effects against human osteosarcoma cells and promoted apoptosis through suppressing Wnt/β-catenin signaling pathway. These results indicated that EVO may be regarded as a new approach for osteosarcoma treatment.
format Online
Article
Text
id pubmed-7196244
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher Dove
record_format MEDLINE/PubMed
spelling pubmed-71962442020-05-18 Evodiamine Exerts Anticancer Effects Against 143B and MG63 Cells Through the Wnt/β-Catenin Signaling Pathway Yang, Shengdong Chen, Jin Tan, Tao Wang, Nan Huang, Yanran Wang, Yuping Yuan, Xiaohui Zhang, Ping Luo, Jinyong Luo, Xiaoji Cancer Manag Res Original Research BACKGROUND: Osteosarcoma is the most common primary malignant bone neoplasm and is associated with abysmal prognosis. There are limitations of current treatment methods. Therefore, developing new agents to treat osteosarcoma is exceptionally urgent. AIM: This study aimed to evaluate the anticancer effects of evodiamine (EVO) on osteosarcoma cells and, meanwhile, to investigate the underlying mechanisms involved. MATERIALS AND METHODS: The effect of EVO on the proliferation of osteosarcoma was detected by MTT assay, crystal violet assay and colony formation assay. The effects of EVO on the migration and invasion of osteosarcoma were detected by wound-healing assay and transwell assay. The effect of EVO on apoptosis of osteosarcoma was measured by Hoechst 33258 staining and cell cycle assay. The protein expression levels were detected by Western blotting assay. The activity of Wnt/β-Catenin signaling pathway was detected by luciferase reporter assay and Western blotting assay. RESULTS: According to MTT, crystal violet and colony formation assay results, EVO significantly inhibited the cell proliferation in a dose-dependent manner. Hoechst 33258 staining assay revealed that EVO induced cell apoptosis in a concentration-dependent manner. Moreover, EVO inhibited the migration and invasion of the osteosarcoma cells. Mechanistic studies revealed that EVO suppresses metastatic through suppressing epithelial–mesenchymal transition (EMT) as indicated by elevating the expression of epithelial marker E‐cadherin and reducing the expression of mesenchymal markers N‐cadherin and vimentin, as well as EMT transcription factors Snail and MMPs. Subsequently, EVO induced cell cycle arrest at the G2/M phase that correlated with reduced levels of cyclin D1 protein, while the apoptotic effects of EVO were associated with the upregulation of Bax and Bad and a decrease in Bcl-2 protein levels. Furthermore, EVO exerted the anticancer effects by suppressing Wnt/β-catenin signal pathway in osteosarcoma cells. CONCLUSION: In summary, EVO exhibited potent anticancer effects against human osteosarcoma cells and promoted apoptosis through suppressing Wnt/β-catenin signaling pathway. These results indicated that EVO may be regarded as a new approach for osteosarcoma treatment. Dove 2020-04-28 /pmc/articles/PMC7196244/ /pubmed/32425601 http://dx.doi.org/10.2147/CMAR.S238093 Text en © 2020 Yang et al. http://creativecommons.org/licenses/by-nc/3.0/ This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php).
spellingShingle Original Research
Yang, Shengdong
Chen, Jin
Tan, Tao
Wang, Nan
Huang, Yanran
Wang, Yuping
Yuan, Xiaohui
Zhang, Ping
Luo, Jinyong
Luo, Xiaoji
Evodiamine Exerts Anticancer Effects Against 143B and MG63 Cells Through the Wnt/β-Catenin Signaling Pathway
title Evodiamine Exerts Anticancer Effects Against 143B and MG63 Cells Through the Wnt/β-Catenin Signaling Pathway
title_full Evodiamine Exerts Anticancer Effects Against 143B and MG63 Cells Through the Wnt/β-Catenin Signaling Pathway
title_fullStr Evodiamine Exerts Anticancer Effects Against 143B and MG63 Cells Through the Wnt/β-Catenin Signaling Pathway
title_full_unstemmed Evodiamine Exerts Anticancer Effects Against 143B and MG63 Cells Through the Wnt/β-Catenin Signaling Pathway
title_short Evodiamine Exerts Anticancer Effects Against 143B and MG63 Cells Through the Wnt/β-Catenin Signaling Pathway
title_sort evodiamine exerts anticancer effects against 143b and mg63 cells through the wnt/β-catenin signaling pathway
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7196244/
https://www.ncbi.nlm.nih.gov/pubmed/32425601
http://dx.doi.org/10.2147/CMAR.S238093
work_keys_str_mv AT yangshengdong evodiamineexertsanticancereffectsagainst143bandmg63cellsthroughthewntbcateninsignalingpathway
AT chenjin evodiamineexertsanticancereffectsagainst143bandmg63cellsthroughthewntbcateninsignalingpathway
AT tantao evodiamineexertsanticancereffectsagainst143bandmg63cellsthroughthewntbcateninsignalingpathway
AT wangnan evodiamineexertsanticancereffectsagainst143bandmg63cellsthroughthewntbcateninsignalingpathway
AT huangyanran evodiamineexertsanticancereffectsagainst143bandmg63cellsthroughthewntbcateninsignalingpathway
AT wangyuping evodiamineexertsanticancereffectsagainst143bandmg63cellsthroughthewntbcateninsignalingpathway
AT yuanxiaohui evodiamineexertsanticancereffectsagainst143bandmg63cellsthroughthewntbcateninsignalingpathway
AT zhangping evodiamineexertsanticancereffectsagainst143bandmg63cellsthroughthewntbcateninsignalingpathway
AT luojinyong evodiamineexertsanticancereffectsagainst143bandmg63cellsthroughthewntbcateninsignalingpathway
AT luoxiaoji evodiamineexertsanticancereffectsagainst143bandmg63cellsthroughthewntbcateninsignalingpathway