Introduction: Compelling evidence has highlighted the complex pleiotropic functions elicited by the melatonin in cancer cells. Melatonin behaves as a 'smart killer', i.e., modulating anti-apoptotic processes in normal cells, and triggering pro-apoptotic signals in cancer cells. Areas covered: Melatonin induces programmed cell death in a wide range of different tumors (breast, gastro-intestinal, hematological, prostate, osteosarcoma, melanoma, kidney, etc.). Mechanisms of action and molecular pathways involved in pro-apoptotic processes under melatonin treatment are discussed. Expert opinion: Melatonin involvement in apoptotic processes is a new and relevant field of investigation. Even in tumor models unresponsive to melatonin alone, this hormone can significantly amplify the cytostatic and the cytotoxic effects triggered by other compounds or conventional drugs. We are far from having a satisfactory understanding about how and when melatonin exerts its beneficial effects. Melatonin in the nanomolar range activates the intrinsic and/or the extrinsic apoptotic pathway in cancer cells, namely through an increase in the p53/MDM2p ratio and downregulation of Sirt1. This finding is of great relevance since there is intense research ongoing to identify nontoxic feasible inhibitors of MDM2 and Sirt1. Melatonin should be evaluated for the management of those cancers where both of these are overexpressed and functionally strategic. © 2013 Informa UK, Ltd.

Molecular mechanisms of the pro-apoptotic actions of melatonin in cancer: A review / Bizzarri, Mariano; Proietti, Sara; Cucina, Alessandra; Russel J., Reiter. - In: EXPERT OPINION ON THERAPEUTIC TARGETS. - ISSN 1472-8222. - STAMPA. - 17:12(2013), pp. 1483-1496. [10.1517/14728222.2013.834890]

Molecular mechanisms of the pro-apoptotic actions of melatonin in cancer: A review

BIZZARRI, Mariano;PROIETTI, SARA;CUCINA, Alessandra;
2013

Abstract

Introduction: Compelling evidence has highlighted the complex pleiotropic functions elicited by the melatonin in cancer cells. Melatonin behaves as a 'smart killer', i.e., modulating anti-apoptotic processes in normal cells, and triggering pro-apoptotic signals in cancer cells. Areas covered: Melatonin induces programmed cell death in a wide range of different tumors (breast, gastro-intestinal, hematological, prostate, osteosarcoma, melanoma, kidney, etc.). Mechanisms of action and molecular pathways involved in pro-apoptotic processes under melatonin treatment are discussed. Expert opinion: Melatonin involvement in apoptotic processes is a new and relevant field of investigation. Even in tumor models unresponsive to melatonin alone, this hormone can significantly amplify the cytostatic and the cytotoxic effects triggered by other compounds or conventional drugs. We are far from having a satisfactory understanding about how and when melatonin exerts its beneficial effects. Melatonin in the nanomolar range activates the intrinsic and/or the extrinsic apoptotic pathway in cancer cells, namely through an increase in the p53/MDM2p ratio and downregulation of Sirt1. This finding is of great relevance since there is intense research ongoing to identify nontoxic feasible inhibitors of MDM2 and Sirt1. Melatonin should be evaluated for the management of those cancers where both of these are overexpressed and functionally strategic. © 2013 Informa UK, Ltd.
2013
melatonin; systems biology; apoptosis; sirt1; mdm2; cancer
01 Pubblicazione su rivista::01a Articolo in rivista
Molecular mechanisms of the pro-apoptotic actions of melatonin in cancer: A review / Bizzarri, Mariano; Proietti, Sara; Cucina, Alessandra; Russel J., Reiter. - In: EXPERT OPINION ON THERAPEUTIC TARGETS. - ISSN 1472-8222. - STAMPA. - 17:12(2013), pp. 1483-1496. [10.1517/14728222.2013.834890]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/697116
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