Inhibition of epithelial-mesenchymal transition in response to treatment with metformin and Y27632 in breast cancer cell lines

Camila Leonel, Lívia Carvalho Ferreira, Thaiz Ferraz Borin, Marina Gobbe Moschetta, Gabriela Scavacini Freitas, Michel Raineri Haddad, João Antonio de Camargos Pinto Robles, Debora Aparecida Pires de Campos Zuccari

Research output: Contribution to journalArticle

5 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1113-1125
Number of pages13
JournalAnti-Cancer Agents in Medicinal Chemistry
Volume17
Issue number8
DOIs
StatePublished - Jul 1 2017
Externally publishedYes

Fingerprint

Epithelial-Mesenchymal Transition
Metformin
Breast Neoplasms
Cell Line
Transforming Growth Factor beta
Vimentin
Cadherins
Neoplasms
Cell Movement
Y 27632
Proteins
Neoplasm Metastasis
Pharmaceutical Preparations

Keywords

  • Anticarcinogenic agents
  • Breast cancer
  • EMT
  • Metformin
  • ROCK1
  • TGF-β

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology
  • Cancer Research

Cite this

Inhibition of epithelial-mesenchymal transition in response to treatment with metformin and Y27632 in breast cancer cell lines. / Leonel, Camila; Ferreira, Lívia Carvalho; Borin, Thaiz Ferraz; Moschetta, Marina Gobbe; Freitas, Gabriela Scavacini; Haddad, Michel Raineri; Robles, João Antonio de Camargos Pinto; Zuccari, Debora Aparecida Pires de Campos.

In: Anti-Cancer Agents in Medicinal Chemistry, Vol. 17, No. 8, 01.07.2017, p. 1113-1125.

Research output: Contribution to journalArticle

Leonel, Camila ; Ferreira, Lívia Carvalho ; Borin, Thaiz Ferraz ; Moschetta, Marina Gobbe ; Freitas, Gabriela Scavacini ; Haddad, Michel Raineri ; Robles, João Antonio de Camargos Pinto ; Zuccari, Debora Aparecida Pires de Campos. / Inhibition of epithelial-mesenchymal transition in response to treatment with metformin and Y27632 in breast cancer cell lines. In: Anti-Cancer Agents in Medicinal Chemistry. 2017 ; Vol. 17, No. 8. pp. 1113-1125.
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AU - Ferreira, Lívia Carvalho

AU - Borin, Thaiz Ferraz

AU - Moschetta, Marina Gobbe

AU - Freitas, Gabriela Scavacini

AU - Haddad, Michel Raineri

AU - Robles, João Antonio de Camargos Pinto

AU - Zuccari, Debora Aparecida Pires de Campos

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N2 - 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.

AB - 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.

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