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Int. J. Mol. Sci. 2018, 19(5), 1505; https://doi.org/10.3390/ijms19051505

Melatonin Analogue Antiproliferative and Cytotoxic Effects on Human Prostate Cancer Cells

1
Department of Medical Biotechnology and Translational Medicine, Università degli Studi di Milano, 20122 Milan, Italy
2
Department of Oncology and Hemato-oncology, Università degli Studi di Milano, 20122 Milan, Italy
These authors contributed equally to this work.
*
Author to whom correspondence should be addressed.
Received: 29 April 2018 / Revised: 14 May 2018 / Accepted: 16 May 2018 / Published: 18 May 2018
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Abstract

Melatonin has been indicated as a possible oncostatic agent in different types of cancer, its antiproliferative role being demonstrated in several in vitro and in vivo experimental models of tumors. Specifically, melatonin was proven to inhibit cell growth of both androgen-dependent and independent prostate cancer cells, through various mechanisms. A number of melatonin derivatives have been developed and tested for their role in the prevention and treatment of neoplastic diseases. We recently proved the in vitro and in vivo anticancer activity of UCM 1037, a newly-synthetized melatonin analogue, on melanoma and breast cancer cells. In this study we evaluated UCM 1037 effects on cell proliferation, cell cycle distribution, and cytotoxicity in LNCaP, PC3, DU145, and 22Rv1 prostate cancer cells. We demonstrated significant dose- and time-dependent UCM 1037 antiproliferative effects in androgen-sensitive LNCaP and 22Rv1 cells. Data from flow cytometric studies suggest that UCM 1037 is highly cytotoxic in androgen-sensitive prostate cancer cells, although no substantial increase in the apoptotic cell fraction has been observed. UCM 1037 cytotoxic effects were much less evident in androgen-insensitive PC3 and DU145 cells. Experiments performed to gain insights into the possible mechanism of action of the melatonin derivative revealed that UCM 1037 down-regulates androgen receptor levels and Akt activation in LNCaP and 22Rv1 cells. View Full-Text
Keywords: melatonin analogues; melatonin receptors; anti-cancer drugs; prostate cancer; androgen receptor; Akt melatonin analogues; melatonin receptors; anti-cancer drugs; prostate cancer; androgen receptor; Akt
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Calastretti, A.; Gatti, G.; Lucini, V.; Dugnani, S.; Canti, G.; Scaglione, F.; Bevilacqua, A. Melatonin Analogue Antiproliferative and Cytotoxic Effects on Human Prostate Cancer Cells. Int. J. Mol. Sci. 2018, 19, 1505.

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