Research Papers:
Antiproliferative and pro-apoptotic activity of melatonin analogues on melanoma and breast cancer cells
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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: [email protected]
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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PII: 20124