Melatonin and breast cancer: cellular mechanisms, clinical studies and future perspectives

Abstract

Recent studies have suggested that the pineal hormone melatonin may protect against breast cancer, and the mechanisms underlying its actions are becoming clearer. Melatonin works through receptors and distinct second messenger pathways to reduce cellular proliferation and to induce cellular differentiation. In addition, independently of receptors melatonin can modulate oestrogen-dependent pathways and reduce free-radical formation, thus preventing mutation and cellular toxicity. The fact that melatonin works through a myriad of signalling cascades that are protective to cells makes this hormone a good candidate for use in the clinic for the prevention and/or treatment of cancer. This review summarises cellular mechanisms governing the action of melatonin and then considers the potential use of melatonin in breast cancer prevention and treatment, with an emphasis on improving clinical outcomes.

Melatonin-Induced Oncostasis, Mechanisms and Clinical Relevance

“…In a randomized controlled double-blind clinical trial on 50 patients referred for liver surgery a single preoperative enteral dose of 50 mg/kg melatonin was safe and well tolerated [215]. This underlines the urgent need for large clinical trials in the field of melatonin and cancer [216,217]. …”

Urinary Excretion of Melatonin and Association with Breast Cancer: Meta-Analysis and Review of the Literature

“…Melatonin was also found to protect animals from adriamycin-induced cardiotoxicity, while co-administration of both substances seems to enhance cytotoxic effects, thereby allowing for dose reductions and attenuation of undesirable side effects [16]. However, a variety of receptor-independent anti-carcinogenic effects of melatonin, such as free radical scavenging via antioxidant properties and modulation of immune functions [17], might exist as well that render the drug potentially useful in the treatment of other diseases.…”

Melatonin affects voltage-dependent calcium and potassium currents in MCF-7 cell line cultured either in growth or differentiation medium

“…In particular, by electrophysiological technique, we evaluated the action of melatonin on resting membrane potential and on voltage-dependent ionic channels known to play a role in proliferation (Baglioni et al, 2012;Bertolesi et al, 2002;Currò, 2014;Enomoto et al, 1986;Gamper et al, 2002;Girgert et al, 2009;Grant et al, 2009;Gray et al, 2004;Haren et al, 2010;Kunzelmann, 2005).…”