Basic Mechanisms Involved in the Anti-Cancer Effects of Melatonin

M.      D. Mediavilla; E.      J. Sanchez-Barcelo; D.      X. Tan; L.      Manchester; R.      J. Reiter

doi:10.2174/092986710794183015

Abstract

It is commonly accepted that melatonin (N-acetyl-5-methoxytryptamine), the most relevant pineal secretory product, has oncostatic properties in a wide variety of tumors and, especially, in those identified as being hormone-dependent. The objective of the present article is to offer a global and integrative view of the mechanisms involved in the oncostatic actions of this indoleamine. Due to the wide spectrum of melatonins actions, the mechanisms that may be involved in its ability to counteract tumor growth are varied. These include: a) antioxidant effects; b) regulation of the estrogen receptor expression and transactivation; c) modulation of the enzymes involved in the local synthesis of estrogens; d) modulation of cell cycle and induction of apoptosis; e) inhibition of telomerase activity; f) inhibition of metastasis; g) prevention of circadian disruption; h) antiangiogenesis; i) epigenetic effects; j) stimulation of cell differentiation; and k) activation of the immune system. The data supporting each of these oncostatic actions of melatonin are summarized in this review. Moreover, the list of actions described may not be exhaustive in terms of how melatonin modulates tumor growth.

Keywords: Melatonin, cancer, antioxidant, immunoenhancing, estrogen signalling pathway, angiogenesis, telomerase, metastasis, epigenetic effects, indoleamine, malignant tumors, Neuroendocrin, neoplastic diseases, malignant neoplasias, sarcomas, colorectal cancer, hepatocarcinomas, melanoma, neural tumors, larynx carcinomas, cervical cancer, estrogenic receptor, mitogenic proteins, calmodulin (CaM), osteoblasts, aortic smooth muscle, antiaromatases, anastroxole, exemestrane, letrozole, estrogen sulfotransferases, mesenchymal stem cells, cytodifferentiating effects, cytosolic proteases, apoptotic induced factor, vincristine, ifosfamide, telomerase activity, xenoestrogens, reactive oxygen species, carbonic anhydrase IX, suprachiasmatic nuclei, E-cadherin, 1-integrin, lymphoid organs, lymphocytes, pinealectomy, epidermal growth factor receptor (EGFR), mitogenactivated protein kinase (MAPK), 13-hydroxyoctadecadienoic acid, neuroendocrine-reproductive, neoplasias