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Berberine Inhibits the Metastatic Ability of Prostate Cancer Cells by Suppressing Epithelial-to-Mesenchymal Transition (EMT)-Associated Genes with Predictive and Prognostic Relevance
Background: Over 70% of cancer metastasis from prostate cancer develops bone metastases that are not sensitive to hormonal therapy, radiation therapy, or chemotherapy. The epithelial-to-mesenchymal transition (EMT) genetic program is implicated as a significant contributor to prostate cancer progres...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Ivyspring International Publisher
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4278877/ https://www.ncbi.nlm.nih.gov/pubmed/25552920 http://dx.doi.org/10.7150/ijms.9982 |
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author | Liu, Chia-Hung Tang, Wan-Chun Sia, Peik Huang, Chi-Chen Yang, Pei-Ming Wu, Ming-Heng Lai, I-Lu Lee, Kuen-Haur |
author_facet | Liu, Chia-Hung Tang, Wan-Chun Sia, Peik Huang, Chi-Chen Yang, Pei-Ming Wu, Ming-Heng Lai, I-Lu Lee, Kuen-Haur |
author_sort | Liu, Chia-Hung |
collection | PubMed |
description | Background: Over 70% of cancer metastasis from prostate cancer develops bone metastases that are not sensitive to hormonal therapy, radiation therapy, or chemotherapy. The epithelial-to-mesenchymal transition (EMT) genetic program is implicated as a significant contributor to prostate cancer progression. As such, targeting the EMT represents an important therapeutic strategy for preventing or treating prostate cancer metastasis. Berberine is a natural alkaloid with significant antitumor activities against many types of cancer cells. In this study, we investigated the molecular mechanism by which berberine represses the metastatic potential of prostate cancer. Methods: The effects of berberine on cell migration and invasion were determined by transwell migration assay and Matrigel invasion assay. Expressions of EMT-related genes were determined by an EMT PCR Array and a quantitative RT-PCR. The prognostic relevance of berberine's modulation of EMT-related genes in prostate cancer was evaluated using Kaplan-Meier survival analysis. Results: Berberine exerted inhibitory effects on the migratory and invasive abilities of highly metastatic prostate cancer cells. These inhibitory effects of berberine resulted in significant repression of a panel of mesenchymal genes that regulate the developmental EMT. Among EMT-related genes downregulated by berberine, high BMP7, NODAL and Snail gene expressions of metastatic prostate cancer tissues were associated with shorter survival of prostate cancer patients and provide potential therapeutic interventions. Conclusions: We concluded that berberine should be developed as a pharmacological agent for use in combination with other anticancer drug for treating metastatic prostate cancer. |
format | Online Article Text |
id | pubmed-4278877 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Ivyspring International Publisher |
record_format | MEDLINE/PubMed |
spelling | pubmed-42788772015-01-01 Berberine Inhibits the Metastatic Ability of Prostate Cancer Cells by Suppressing Epithelial-to-Mesenchymal Transition (EMT)-Associated Genes with Predictive and Prognostic Relevance Liu, Chia-Hung Tang, Wan-Chun Sia, Peik Huang, Chi-Chen Yang, Pei-Ming Wu, Ming-Heng Lai, I-Lu Lee, Kuen-Haur Int J Med Sci Research Paper Background: Over 70% of cancer metastasis from prostate cancer develops bone metastases that are not sensitive to hormonal therapy, radiation therapy, or chemotherapy. The epithelial-to-mesenchymal transition (EMT) genetic program is implicated as a significant contributor to prostate cancer progression. As such, targeting the EMT represents an important therapeutic strategy for preventing or treating prostate cancer metastasis. Berberine is a natural alkaloid with significant antitumor activities against many types of cancer cells. In this study, we investigated the molecular mechanism by which berberine represses the metastatic potential of prostate cancer. Methods: The effects of berberine on cell migration and invasion were determined by transwell migration assay and Matrigel invasion assay. Expressions of EMT-related genes were determined by an EMT PCR Array and a quantitative RT-PCR. The prognostic relevance of berberine's modulation of EMT-related genes in prostate cancer was evaluated using Kaplan-Meier survival analysis. Results: Berberine exerted inhibitory effects on the migratory and invasive abilities of highly metastatic prostate cancer cells. These inhibitory effects of berberine resulted in significant repression of a panel of mesenchymal genes that regulate the developmental EMT. Among EMT-related genes downregulated by berberine, high BMP7, NODAL and Snail gene expressions of metastatic prostate cancer tissues were associated with shorter survival of prostate cancer patients and provide potential therapeutic interventions. Conclusions: We concluded that berberine should be developed as a pharmacological agent for use in combination with other anticancer drug for treating metastatic prostate cancer. Ivyspring International Publisher 2015-01-01 /pmc/articles/PMC4278877/ /pubmed/25552920 http://dx.doi.org/10.7150/ijms.9982 Text en © Ivyspring International Publisher. This is an open-access article distributed under the terms of the Creative Commons License (http://creativecommons.org/licenses/by-nc-nd/3.0/). Reproduction is permitted for personal, noncommercial use, provided that the article is in whole, unmodified, and properly cited. |
spellingShingle | Research Paper Liu, Chia-Hung Tang, Wan-Chun Sia, Peik Huang, Chi-Chen Yang, Pei-Ming Wu, Ming-Heng Lai, I-Lu Lee, Kuen-Haur Berberine Inhibits the Metastatic Ability of Prostate Cancer Cells by Suppressing Epithelial-to-Mesenchymal Transition (EMT)-Associated Genes with Predictive and Prognostic Relevance |
title | Berberine Inhibits the Metastatic Ability of Prostate Cancer Cells by Suppressing Epithelial-to-Mesenchymal Transition (EMT)-Associated Genes with Predictive and Prognostic Relevance |
title_full | Berberine Inhibits the Metastatic Ability of Prostate Cancer Cells by Suppressing Epithelial-to-Mesenchymal Transition (EMT)-Associated Genes with Predictive and Prognostic Relevance |
title_fullStr | Berberine Inhibits the Metastatic Ability of Prostate Cancer Cells by Suppressing Epithelial-to-Mesenchymal Transition (EMT)-Associated Genes with Predictive and Prognostic Relevance |
title_full_unstemmed | Berberine Inhibits the Metastatic Ability of Prostate Cancer Cells by Suppressing Epithelial-to-Mesenchymal Transition (EMT)-Associated Genes with Predictive and Prognostic Relevance |
title_short | Berberine Inhibits the Metastatic Ability of Prostate Cancer Cells by Suppressing Epithelial-to-Mesenchymal Transition (EMT)-Associated Genes with Predictive and Prognostic Relevance |
title_sort | berberine inhibits the metastatic ability of prostate cancer cells by suppressing epithelial-to-mesenchymal transition (emt)-associated genes with predictive and prognostic relevance |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4278877/ https://www.ncbi.nlm.nih.gov/pubmed/25552920 http://dx.doi.org/10.7150/ijms.9982 |
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