Abstract
Background: ROCK-1 expression is associated with the malignant character of tumors, while inhibiting this molecule results in a significant suppression of tumor metastasis. Likewise, transforming growth factor beta (TGF-β) is associated with this malignancy by having the ability to induce epithelial-mesenchymal transition (EMT). Metformin, a drug used in the treatment of diabetes, has previously been shown to inhibit EMT in breast cancer cells.
Objective: The aim of this study is to evaluate the TGF-β1 action model for induction of EMT and the action of metformin and ROCK-1 inhibitor (Y27632) in EMT process in breast cancer cell lines. Method: MCF-7 and MDA-MB-231 cell lines were treated with metformin and Y27632, after induction of EMT by TGF-β1, to examine the effects on cell migration as well as the protein expression of the ROCK-1 markers, vimentin, E-cadherin, CD44 and CD24 by immunocitochemistry. Results: There was a lower protein expression of ROCK-1, vimentin, CD44 and CD24 in both cell lines after treatment with metformin and Y27632. In MDA-MB-231 cells, E-cadherin expression was increased in all treatment groups. Treatment of MDA-MB-231 cell line with metformin and Y27632 significantly reduced the invasion of these cells. Conclusion: This study confirms the benefits of metformin and Y27632 as potential therapeutic agents in mammary tumors, by blocking EMT process and metastatic potential.Keywords: Breast cancer, anticarcinogenic agents, TGF-β, EMT, ROCK1, metformin.
Graphical Abstract
Anti-Cancer Agents in Medicinal Chemistry
Title:Inhibition of Epithelial-mesenchymal Transition in Response to Treatment with Metformin and Y27632 in Breast Cancer Cell Lines
Volume: 17 Issue: 8
Author(s): Camila Leonel, Lívia Carvalho Ferreira, Thaiz Ferraz Borin, Marina Gobbe Moschetta, Gabriela Scavacini Freitas, Michel Raineri Haddad, João Antonio de Camargos Pinto Robles and Debora Aparecida Pires de Campos Zuccari*
Affiliation:
- Laboratory of Molecular Investigation of Cancer (LIMC), FAMERP – Faculdade de Medicina de Sao Jose do Rio Preto, Av. Brigadeiro Faria Lima 5416, 15090.000 Sao Jose do Rio Preto, Sao Paulo, Brazil,Brazil
Keywords: Breast cancer, anticarcinogenic agents, TGF-β, EMT, ROCK1, metformin.
Abstract: Background: ROCK-1 expression is associated with the malignant character of tumors, while inhibiting this molecule results in a significant suppression of tumor metastasis. Likewise, transforming growth factor beta (TGF-β) is associated with this malignancy by having the ability to induce epithelial-mesenchymal transition (EMT). Metformin, a drug used in the treatment of diabetes, has previously been shown to inhibit EMT in breast cancer cells.
Objective: The aim of this study is to evaluate the TGF-β1 action model for induction of EMT and the action of metformin and ROCK-1 inhibitor (Y27632) in EMT process in breast cancer cell lines. Method: MCF-7 and MDA-MB-231 cell lines were treated with metformin and Y27632, after induction of EMT by TGF-β1, to examine the effects on cell migration as well as the protein expression of the ROCK-1 markers, vimentin, E-cadherin, CD44 and CD24 by immunocitochemistry. Results: There was a lower protein expression of ROCK-1, vimentin, CD44 and CD24 in both cell lines after treatment with metformin and Y27632. In MDA-MB-231 cells, E-cadherin expression was increased in all treatment groups. Treatment of MDA-MB-231 cell line with metformin and Y27632 significantly reduced the invasion of these cells. Conclusion: This study confirms the benefits of metformin and Y27632 as potential therapeutic agents in mammary tumors, by blocking EMT process and metastatic potential.Export Options
About this article
Cite this article as:
Leonel Camila, Ferreira Carvalho Lívia, Borin Ferraz Thaiz, Moschetta Gobbe Marina, Freitas Scavacini Gabriela, Haddad Raineri Michel, de Camargos Pinto Robles Antonio João and Aparecida Pires de Campos Zuccari Debora*, Inhibition of Epithelial-mesenchymal Transition in Response to Treatment with Metformin and Y27632 in Breast Cancer Cell Lines, Anti-Cancer Agents in Medicinal Chemistry 2017; 17 (8) . https://dx.doi.org/10.2174/1871520617666170102153954
DOI https://dx.doi.org/10.2174/1871520617666170102153954 |
Print ISSN 1871-5206 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5992 |
![](/images/wayfinder.jpg)
- Author Guidelines
- Bentham Author Support Services (BASS)
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
HER2-Mediated Anticancer Drug Delivery: Strategies to Prepare Targeting Ligands Highly Specific for the Receptor
Current Medicinal Chemistry Subject Index To Volume 7
Current Pharmaceutical Design Gut-liver Axis and Microbiota in NAFLD: Insight Pathophysiology for Novel Therapeutic Target
Current Pharmaceutical Design Emerging Anabolic Treatments in Osteoporosis
Current Drug Safety Nutrition in Adult Patients with Inflammatory Bowel Disease
Current Drug Targets Targeting Cell Necroptosis and Apoptosis Induced by Shikonin via Receptor Interacting Protein Kinases in Estrogen Receptor Positive Breast Cancer Cell Line, MCF-7
Anti-Cancer Agents in Medicinal Chemistry Prodrug Design Targeting Intestinal PepT1 for Improved Oral Absorption: Design and Performance
Current Drug Metabolism H+-myo-Inositol Transporter SLC2A13 as a Potential Marker for Cancer Stem Cells in an Oral Squamous Cell Carcinoma
Current Cancer Drug Targets Inhibitory Effect of Fruit Juices on the Doxorubicin Metabolizing Activity of Carbonyl Reductase 1
Drug Metabolism Letters Insights on Melatonin as an Active Pharmacological Molecule in Cancer Prevention: What’s New?
Current Medicinal Chemistry The Antidepressant-like Effects of Estrogen-mediated Ghrelin
Current Neuropharmacology Colon Targeted Rifaximin Nanosuspension for the Treatment of Inflammatory Bowel Disease (IBD)
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry Fused Xanthone Derivatives as Antiproliferative Agents
Anti-Cancer Agents in Medicinal Chemistry Coagulation and Cancer Therapy: The Potential of Natural Compounds
Current Genomics New Biomarkers for Colon Cancer Diagnosis: A Review of Recent Patents
Recent Patents on Biomarkers Flax Terpenoid Pathway as a Source of Health Promoting Compounds
Mini-Reviews in Medicinal Chemistry CNS Drug Development – Lost in Translation?
Mini-Reviews in Medicinal Chemistry Leptin and Inflammation
Current Immunology Reviews (Discontinued) Gallic Acid and Gallic Acid Derivatives: Effects on Drug Metabolizing Enzymes
Current Drug Metabolism Strategies for the Assessment of Metabolic Profiles of Steroid Hormones in View of Diagnostics and Drug Monitoring: Analytical Problems and Challenges
Current Drug Metabolism