Melatonin Analogues May Have Antitumor Properties in Melanoma and Breast Cancer
Previous studies have demonstrated that melatonin and its analogues, in addition to their ability to regulate circadian rhythms, may exhibit cytotoxic activity via various cellular mechanisms.
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Melatonin derivatives may have antitumorigenic effects against melanoma and breast cancer cells, according to a poster presented at the 35th Annual Chemotherapy Foundation Symposium in New York.1
Previous studies have demonstrated that melatonin and its analogues, in addition to their ability to regulate circadian rhythms, may exhibit cytotoxic activity via various cellular mechanisms. For this study, researchers investigated the in vitro and in vivo effects of melatonin derivatives on cancer cells.
New melatonin analogues (UCM 976, UCM 1032, UCM 1033, UCM 1037) that target the MT1 and MT2 membrane receptors were derived from previously existing indole melatonin receptor ligands. The new indole analogues exhibited an ability to inhibit DX3 melanoma cell proliferation and MCF-7 and MDA-MB231 breast cancer cells in a dose- and time-dependent manner in viability assays. Further analysis revealed that UCM 1037 at concentrations of 0.1 mM exhibited antiproliferative and cytotoxic activity in breast cancer cells.
In vivo testing in xenograft mice models confirmed that UCM 1037 suppressed DX3 tumor growth, and also demonstrated greater inhibitory activity compared with just melatonin at the same dose (16 mg/kg).
Using a Western blot analysis, study authors further examined the changes in levels of different proteins in cancer cell lines after treatment with melatonin analogues. Findings suggested that UCM 1037 induces caspase 3, a protein found to be associated with apoptotic activity in DX3 melanoma and MDA-MB231 breast cancer cells. Treatment with UCM 1037 led to a decrease in activation of both Akt and MAPK pathways in breast cancer cells.
The authors concluded, “[t]he study of synergistic relationships between melatonin analogues and anticancer drugs is a promising field, and these compounds could significantly strengthen the cytostatic and the cytotoxic effects triggered by conventional antineoplastic drugs.”
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- Bevilacqua A, Gatti G, Lucini V, et al. Antitumor activity of new melatonin derivatives on melanoma and breast cancer cells. Poster presented at: 35th Annual Chemotherapy Foundation Symposium; New York; November 8-10, 2017. Poster 552.