International Journal of Medical Sciences

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15 December 2017

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Int J Med Sci 2015; 12(1):63-71. doi:10.7150/ijms.9982

Research Paper

Berberine Inhibits the Metastatic Ability of Prostate Cancer Cells by Suppressing Epithelial-to-Mesenchymal Transition (EMT)-Associated Genes with Predictive and Prognostic Relevance

Chia-Hung Liu1, Wan-Chun Tang2, Peik Sia2, Chi-Chen Huang3, Pei-Ming Yang2, Ming-Heng Wu4, I-Lu Lai5, Kuen-Haur Lee2 ✉

1. Department of Urology, Taipei Medical University-Shuang Ho Hospital, New Taipei City, Taiwan;
2. Graduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan;
3. The PhD Program for Neural Regenerative Medicine, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan;
4. The PhD Program for Translational Medicine, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan.
5. Division of Medicinal Chemistry, College of Pharmacy and Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA.

Abstract

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.

Keywords: Berberine, EMT, Prostate cancer.

This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) License. See http://ivyspring.com/terms for full terms and conditions.
How to cite this article:
Liu CH, Tang WC, Sia P, Huang CC, Yang PM, Wu MH, Lai IL, Lee KH. Berberine Inhibits the Metastatic Ability of Prostate Cancer Cells by Suppressing Epithelial-to-Mesenchymal Transition (EMT)-Associated Genes with Predictive and Prognostic Relevance. Int J Med Sci 2015; 12(1):63-71. doi:10.7150/ijms.9982. Available from http://www.medsci.org/v12p0063.htm