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.
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 |
Call for Papers in Thematic Issues
Induction of cell death in cancer cells by modulating telomerase activity using small molecule drugs
Telomeres are distinctive but short stretches present at the corners of chromosomes and aid in stabilizing chromosomal makeup. Resynthesis of telomeres supported by the activity of reverse transcriptase ribonucleoprotein complex telomerase. There is no any telomerase activity in human somatic cells, but the stem cells and germ cells undergone telomerase ...read more
Role of natural compounds as anti anti-cancer agents
Cancer is considered the leading cause of worldwide mortality, accounting for nearly 10 million deaths in 2022. Cancer outcome can be improved through an appropriate screening and early detection and through an efficient clinical treatment. Chemotherapy remains an important approach in treatment o f several types of cancers, even though ...read more
Signaling and enzymatic modulators in cancer treatment
Cancer accounts for nearly 10 million deaths in 2022 and is considered the leading cause of worldwide mortality. Cancer outcome can be improved through an appropriate screening and early detection and through an efficient clinical treatment. Chemotherapy, radiotherapy and surgery are the most important approach for the treatment of several ...read more
- Author Guidelines
- 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
-
Apoptosis and Autophagy Induction As Mechanism of Cancer Prevention by Naturally Occurring Dietary Agents
Current Drug Targets Snake Venom Peptides and Low Mass Proteins: Molecular Tools and Therapeutic Agents
Current Medicinal Chemistry Applications of Nucleic Acid Drugs for Organ Transplantation
Current Topics in Medicinal Chemistry Interrelationships Among Gut Microbiota and Host: Paradigms, Role in Neurodegenerative Diseases and Future Prospects
CNS & Neurological Disorders - Drug Targets Meet Our Editorial Board Member
Mini-Reviews in Medicinal Chemistry Cytotoxicity of Chitosan Ultrafine Nanoshuttles on the MCF-7 Cell Line as a Surrogate Model for Breast Cancer
Current Drug Delivery Emerging Technologies for Fertility Preservation in Female Patients
Current Women`s Health Reviews Recent Patents Concerning Diagnostic and Therapeutic Applications of Aberrantly Methylated Sequences in Pancreatic Cancer
Recent Patents on DNA & Gene Sequences Small Molecular Inhibitors Targeting Chromatin Regulating Proteins for Cancer
Current Protein & Peptide Science Targeting the Human Epidermal Growth Factor Receptor 2 (HER2) in the Treatment of Breast Cancer: Recent Advances and Future Directions
Reviews on Recent Clinical Trials Inhibitors of Catechol-O-methyltransferase in the Treatment of Neurological Disorders
Central Nervous System Agents in Medicinal Chemistry β -Glucans and their Applications in Cancer Therapy: Focus on human studies
Anti-Cancer Agents in Medicinal Chemistry Hepato and Cardiotoxicity of Chemotherapeutic Treatment Evaluated by Means of Small Animal Imaging
Anti-Cancer Agents in Medicinal Chemistry Current and Future Perspectives on the Major Depressive Disorder: Focus on the New Multimodal Antidepressant Vortioxetine
CNS & Neurological Disorders - Drug Targets The Delivery of Biologically Active (Therapeutic) Peptides and Proteins into Cells
Current Medicinal Chemistry Reduction of Doxorubicin-Induced Cardiotoxicity Using Nanocarriers: A Review
Current Drug Metabolism A Comprehensive Overview of the Synthesis of Tetrahydrocarbazoles and its Biological Properties
Mini-Reviews in Organic Chemistry Current Strategy for Cisplatin Delivery
Current Cancer Drug Targets Chloroform Fraction of Methanolic Extract of Seeds of <i>Annona muricata</i> Induce S Phase Arrest and ROS Dependent Caspase Activated Mitochondria-Mediated Apoptosis in Triple-Negative Breast Cancer
Anti-Cancer Agents in Medicinal Chemistry Medicinal Perspective of Indole Derivatives: Recent Developments and Structure-Activity Relationship Studies
Current Drug Targets