Melatonin decreases breast cancer metastasis by modulating ROCK-1 expression.
J Pineal Res. 2015 Aug 21. Epub 2015 Aug 21. PMID: 26292662
Thaiz Ferraz Borin
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, anti-metastatic, and antiangiogenic effects and can modulate ROCK-1 expression. Metastatic and non-metastatic 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 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 weeks. The metastases were evaluated by X-ray computed tomography (CT) and single photon emission computed tomography (SPECT) and by immunohistochemistry for ROCK-1 and cytokeratin proteins. Melatonin and Y27632 treatments reduced cell viability, invasion/migration of both cell lines and decreased ROCK-1 gene expression in metastatic cells and protein expression in non-metastatic 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. This article is protected by copyright. All rights reserved.