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

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Published on Monday, 29 February 2016

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.

 

 

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See also:

- About Melatonin;

- Evaluation of the safety and efficacy of the first-line treatment with somatostatin combined with melatonin, retinoids, vitamin D3, and low doses of cyclophosphamide in 20 cases of breast cancer: a preliminary report;

- The Di Bella Method (DBM) improved survival, objective response and performance status in a retrospective observational clinical study on 122 cases of breast cancer;

- Complete objective response to biological therapy of plurifocal breast carcinoma.