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Jatrorrhizine inhibits colorectal carcinoma proliferation and metastasis through Wnt/β-catenin signaling pathway and epithelial–mesenchymal transition

PURPOSE: Jatrorrhizine (JAT) is a natural protoberberine alkaloid, possesses detoxification, bactericidal and hypoglycemic activities. However, its anti-cancer mechanism is not clear. This study aimed to investigate the mechanism of JAT through which inhibits colorectal cancer in HCT-116 and HT-29 c...

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Autores principales: Wang, Pan, Gao, Xiao-Yan, Yang, Si-Qian, Sun, Zhi-Xin, Dian, Lu-Lu, Qasim, Muhammad, Phyo, Aung Thu, Liang, Zong-Suo, Sun, Yan-Fang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6627180/
https://www.ncbi.nlm.nih.gov/pubmed/31371920
http://dx.doi.org/10.2147/DDDT.S207315
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author Wang, Pan
Gao, Xiao-Yan
Yang, Si-Qian
Sun, Zhi-Xin
Dian, Lu-Lu
Qasim, Muhammad
Phyo, Aung Thu
Liang, Zong-Suo
Sun, Yan-Fang
author_facet Wang, Pan
Gao, Xiao-Yan
Yang, Si-Qian
Sun, Zhi-Xin
Dian, Lu-Lu
Qasim, Muhammad
Phyo, Aung Thu
Liang, Zong-Suo
Sun, Yan-Fang
author_sort Wang, Pan
collection PubMed
description PURPOSE: Jatrorrhizine (JAT) is a natural protoberberine alkaloid, possesses detoxification, bactericidal and hypoglycemic activities. However, its anti-cancer mechanism is not clear. This study aimed to investigate the mechanism of JAT through which inhibits colorectal cancer in HCT-116 and HT-29 cells. METHODS: MTT assay and colony formation assay were used to check the cell proliferation ability. Cell apoptosis and cell cycle were measured by Hoechst 33342 staining and flow cytometry, respectively. Cell migration and invasion were detected by scratch wound healing assay and trans-well assay, respectively. Further, expression of related proteins was examined via Western blotting and the in vivo anti-cancer effect of JAT was confirmed by nude mice xenograft model. RESULTS: The research showed that JAT inhibited the proliferation of HCT-116 and HT-29 cells with IC(50) values of 6.75±0.29 μM and 5.29±0.13 μM, respectively, for 72 hrs. It has also showed a time dependently, cell cycle arrested in S phase, promoted cell apoptosis and suppressed cell migration and invasion. In addition, JAT inhibited Wnt signaling pathway by reducing β-catenin and increasing GSK-3β expressions. Increased expression of E-cadherin, while decreased N-cadherin, indicating that JAT treatment suppressed the process of cell epithelial–mesenchymal transition (EMT). In HCT-116 nude mice xenograft model, JAT inhibited tumor growth and metastasis, and induced apoptosis of tumor cells. CONCLUSION: This study demonstrated that JAT efficiently inhibited colorectal cancer cells growth and metastasis, which provides a new point for clinical treatment of colorectal cancer.
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spelling pubmed-66271802019-08-01 Jatrorrhizine inhibits colorectal carcinoma proliferation and metastasis through Wnt/β-catenin signaling pathway and epithelial–mesenchymal transition Wang, Pan Gao, Xiao-Yan Yang, Si-Qian Sun, Zhi-Xin Dian, Lu-Lu Qasim, Muhammad Phyo, Aung Thu Liang, Zong-Suo Sun, Yan-Fang Drug Des Devel Ther Original Research PURPOSE: Jatrorrhizine (JAT) is a natural protoberberine alkaloid, possesses detoxification, bactericidal and hypoglycemic activities. However, its anti-cancer mechanism is not clear. This study aimed to investigate the mechanism of JAT through which inhibits colorectal cancer in HCT-116 and HT-29 cells. METHODS: MTT assay and colony formation assay were used to check the cell proliferation ability. Cell apoptosis and cell cycle were measured by Hoechst 33342 staining and flow cytometry, respectively. Cell migration and invasion were detected by scratch wound healing assay and trans-well assay, respectively. Further, expression of related proteins was examined via Western blotting and the in vivo anti-cancer effect of JAT was confirmed by nude mice xenograft model. RESULTS: The research showed that JAT inhibited the proliferation of HCT-116 and HT-29 cells with IC(50) values of 6.75±0.29 μM and 5.29±0.13 μM, respectively, for 72 hrs. It has also showed a time dependently, cell cycle arrested in S phase, promoted cell apoptosis and suppressed cell migration and invasion. In addition, JAT inhibited Wnt signaling pathway by reducing β-catenin and increasing GSK-3β expressions. Increased expression of E-cadherin, while decreased N-cadherin, indicating that JAT treatment suppressed the process of cell epithelial–mesenchymal transition (EMT). In HCT-116 nude mice xenograft model, JAT inhibited tumor growth and metastasis, and induced apoptosis of tumor cells. CONCLUSION: This study demonstrated that JAT efficiently inhibited colorectal cancer cells growth and metastasis, which provides a new point for clinical treatment of colorectal cancer. Dove 2019-07-08 /pmc/articles/PMC6627180/ /pubmed/31371920 http://dx.doi.org/10.2147/DDDT.S207315 Text en © 2019 Wang 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
Wang, Pan
Gao, Xiao-Yan
Yang, Si-Qian
Sun, Zhi-Xin
Dian, Lu-Lu
Qasim, Muhammad
Phyo, Aung Thu
Liang, Zong-Suo
Sun, Yan-Fang
Jatrorrhizine inhibits colorectal carcinoma proliferation and metastasis through Wnt/β-catenin signaling pathway and epithelial–mesenchymal transition
title Jatrorrhizine inhibits colorectal carcinoma proliferation and metastasis through Wnt/β-catenin signaling pathway and epithelial–mesenchymal transition
title_full Jatrorrhizine inhibits colorectal carcinoma proliferation and metastasis through Wnt/β-catenin signaling pathway and epithelial–mesenchymal transition
title_fullStr Jatrorrhizine inhibits colorectal carcinoma proliferation and metastasis through Wnt/β-catenin signaling pathway and epithelial–mesenchymal transition
title_full_unstemmed Jatrorrhizine inhibits colorectal carcinoma proliferation and metastasis through Wnt/β-catenin signaling pathway and epithelial–mesenchymal transition
title_short Jatrorrhizine inhibits colorectal carcinoma proliferation and metastasis through Wnt/β-catenin signaling pathway and epithelial–mesenchymal transition
title_sort jatrorrhizine inhibits colorectal carcinoma proliferation and metastasis through wnt/β-catenin signaling pathway and epithelial–mesenchymal transition
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6627180/
https://www.ncbi.nlm.nih.gov/pubmed/31371920
http://dx.doi.org/10.2147/DDDT.S207315
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