Oncotarget

Research Papers:

Antiproliferative and pro-apoptotic activity of melatonin analogues on melanoma and breast cancer cells

Giuliana Gatti, Valeria Lucini, Silvana Dugnani, Angela Calastretti, Gilberto Spadoni, Annalida Bedini, Silvia Rivara, Marco Mor, Gianfranco Canti, Francesco Scaglione and Annamaria Bevilacqua _

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Oncotarget. 2017; 8:68338-68353. https://doi.org/10.18632/oncotarget.20124

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Abstract

Giuliana Gatti1,*, Valeria Lucini2,*, Silvana Dugnani2, Angela Calastretti1, Gilberto Spadoni3, Annalida Bedini3, Silvia Rivara4, Marco Mor4, Gianfranco Canti1, Francesco Scaglione2 and Annamaria Bevilacqua1

1Department of Medical Biotechnology and Translational Medicine, Università degli Studi di Milano, Milan, Italy

2Department of Oncology and Hemato-oncology, Università degli Studi di Milano, Milan, Italy

3Department of Biomolecular Sciences, Università degli Studi di Urbino “Carlo Bo”, Urbino, Italy

4Department of Food and Drug, Università degli Studi di Parma, Parma, Italy

*Authors contributed equally to this work

Correspondence to:

Annamaria Bevilacqua, email: annamaria.bevilacqua@unimi.it

Keywords: melatonin analogues, melatonin receptors, anti-cancer drugs, melanoma, breast cancer

Received: April 11, 2017     Accepted: July 29, 2017     Published: August 10, 2017

ABSTRACT

Melatonin plays different physiological functions ranging from the regulation of circadian rhythms to tumor inhibition, owing to its antioxidant, immunomodulatory and anti-aging properties. Due to its pleiotropic functions, melatonin has been shown to elicit cytoprotective processes in normal cells and trigger pro-apoptotic signals in cancer cells. The therapeutic potential of melatonin analogues prompted us to investigate the in vitro and in vivo antitumor activity of new melatonin derivatives and explore the underlying molecular mechanisms. The experiments revealed that the new melatonin analogues inhibited the growth of melanoma and breast cancer cells in a dose- and time-dependent manner. In addition, our results indicated that melatonin derivative UCM 1037 could induce apoptosis in melanoma and breast cancer cells, as well as cell necrosis, in MCF-7. Together, apoptosis and necrosis could be two possible mechanisms to explain the cytotoxic effect of the melatonin analogue against cancer cells. The suppression of tumor growth by the melatonin analogues was further demonstrated in vivo in a xenograft mice model. A decrease in the activation of MAPK pathway was observed in all cancer cells following UCM 1037 treatment. Overall, this study describes a promising antitumor compound showing antiproliferative and cytotoxic activity in melanoma and breast cancer cells.


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