Molecular mechanisms of the pro-apoptotic actions of melatonin in cancer

A review

Mariano Bizzarri, Sara Proietti, Alessandra Cucina, Russel J Reiter

Research output: Contribution to journalArticle

93 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1483-1496
Number of pages14
JournalExpert Opinion on Therapeutic Targets
Volume17
Issue number12
DOIs
StatePublished - Dec 2013

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Melatonin
Neoplasms
Cells
Tumors
Expert Testimony
Cytostatic Agents
Cell death
Osteosarcoma
Prostate
Melanoma
Cell Death
Down-Regulation
Hormones
Breast Neoplasms
Kidney
Research

Keywords

  • Apoptosis
  • Cancer
  • MDM2
  • Melatonin
  • Sirt1
  • Systems biology

ASJC Scopus subject areas

  • Drug Discovery
  • Pharmacology
  • Clinical Biochemistry
  • Molecular Medicine

Cite this

Molecular mechanisms of the pro-apoptotic actions of melatonin in cancer : A review. / Bizzarri, Mariano; Proietti, Sara; Cucina, Alessandra; Reiter, Russel J.

In: Expert Opinion on Therapeutic Targets, Vol. 17, No. 12, 12.2013, p. 1483-1496.

Research output: Contribution to journalArticle

Bizzarri, Mariano ; Proietti, Sara ; Cucina, Alessandra ; Reiter, Russel J. / Molecular mechanisms of the pro-apoptotic actions of melatonin in cancer : A review. In: Expert Opinion on Therapeutic Targets. 2013 ; Vol. 17, No. 12. pp. 1483-1496.
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