Melatonin decreases breast cancer metastasis by modulating Rho-associated kinase protein-1 expression

Thaiz Ferraz Borin, Ali Syed Arbab, Gabriela Bottaro Gelaleti, Lívia Carvalho Ferreira, Marina Gobbe Moschetta, Bruna Victorasso Jardim-Perassi, Asm Iskander, Nadimpalli Ravi S. Varma, Adarsh Shankar, Verena Benedick Coimbra, Vanessa Alves Fabri, Juliana Garcia De Oliveira, Debora Aparecida Pires De Campos Zuccari

Research output: Contribution to journalArticle

51 Citations (Scopus)

Abstract

The occurrence of metastasis, an important breast cancer prognostic factor, depends on cell migration/invasion mechanisms, which can be controlled by regulatory and effector molecules such as Rho-associated kinase protein (ROCK-1). Increased expression of this protein promotes tumor growth and metastasis, which can be restricted by ROCK-1 inhibitors. Melatonin has shown oncostatic, antimetastatic, and anti-angiogenic effects and can modulate ROCK-1 expression. Metastatic and nonmetastatic breast cancer cell lines were treated with melatonin as well as with specific ROCK-1 inhibitor (Y27632). Cell viability, cell migration/invasion, and ROCK-1 gene expression and protein expression were determined in vitro. In vivo lung metastasis study was performed using female athymic nude mice treated with either melatonin or Y27832 for 2 and 5 wk. The metastases were evaluated by X-ray computed tomography and single photon emission computed tomography (SPECT) and by immunohistochemistry for ROCK-1 and cytokeratin proteins. Melatonin and Y27632 treatments reduced cell viability and invasion/migration of both cell lines and decreased ROCK-1 gene expression in metastatic cells and protein expression in nonmetastatic cell line. The numbers of 'hot' spots (lung metastasis) identified by SPECT images were significantly lower in treated groups. ROCK-1 protein expression also was decreased in metastatic foci of treated groups. Melatonin has shown to be effective in controlling metastatic breast cancer in vitro and in vivo, not only via inhibition of the proliferation of tumor cells but also through direct antagonism of metastatic mechanism of cells rendered by ROCK-1 inhibition. When Y27632 was used, the effects were similar to those found with melatonin treatment.

Original languageEnglish (US)
Pages (from-to)3-15
Number of pages13
JournalJournal of Pineal Research
Volume60
Issue number1
DOIs
StatePublished - Jan 1 2016

Fingerprint

rho-Associated Kinases
Melatonin
Breast Neoplasms
Neoplasm Metastasis
Proteins
Nude Mice
Cell Line
Cell Movement
Cell Survival
Gene Expression
Lung
X Ray Computed Tomography
Keratins
Single-Photon Emission-Computed Tomography
Focus Groups
Neoplasms
Immunohistochemistry
Cell Proliferation
Therapeutics
Growth

Keywords

  • 99mTc-tetrofosmin
  • MCF-7 cells
  • MDA-MB-231 cells
  • Rho-associated kinase protein-1 inhibitor
  • breast cancer
  • lung metastasis
  • melatonin
  • single photon emission computed tomography

ASJC Scopus subject areas

  • Endocrinology

Cite this

Borin, T. F., Arbab, A. S., Gelaleti, G. B., Ferreira, L. C., Moschetta, M. G., Jardim-Perassi, B. V., ... Zuccari, D. A. P. D. C. (2016). Melatonin decreases breast cancer metastasis by modulating Rho-associated kinase protein-1 expression. Journal of Pineal Research, 60(1), 3-15. https://doi.org/10.1111/jpi.12270

Melatonin decreases breast cancer metastasis by modulating Rho-associated kinase protein-1 expression. / Borin, Thaiz Ferraz; Arbab, Ali Syed; Gelaleti, Gabriela Bottaro; Ferreira, Lívia Carvalho; Moschetta, Marina Gobbe; Jardim-Perassi, Bruna Victorasso; Iskander, Asm; Varma, Nadimpalli Ravi S.; Shankar, Adarsh; Coimbra, Verena Benedick; Fabri, Vanessa Alves; De Oliveira, Juliana Garcia; Zuccari, Debora Aparecida Pires De Campos.

In: Journal of Pineal Research, Vol. 60, No. 1, 01.01.2016, p. 3-15.

Research output: Contribution to journalArticle

Borin, TF, Arbab, AS, Gelaleti, GB, Ferreira, LC, Moschetta, MG, Jardim-Perassi, BV, Iskander, A, Varma, NRS, Shankar, A, Coimbra, VB, Fabri, VA, De Oliveira, JG & Zuccari, DAPDC 2016, 'Melatonin decreases breast cancer metastasis by modulating Rho-associated kinase protein-1 expression', Journal of Pineal Research, vol. 60, no. 1, pp. 3-15. https://doi.org/10.1111/jpi.12270
Borin, Thaiz Ferraz ; Arbab, Ali Syed ; Gelaleti, Gabriela Bottaro ; Ferreira, Lívia Carvalho ; Moschetta, Marina Gobbe ; Jardim-Perassi, Bruna Victorasso ; Iskander, Asm ; Varma, Nadimpalli Ravi S. ; Shankar, Adarsh ; Coimbra, Verena Benedick ; Fabri, Vanessa Alves ; De Oliveira, Juliana Garcia ; Zuccari, Debora Aparecida Pires De Campos. / Melatonin decreases breast cancer metastasis by modulating Rho-associated kinase protein-1 expression. In: Journal of Pineal Research. 2016 ; Vol. 60, No. 1. pp. 3-15.
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