Melatonin modulates tumor metabolism and mitigates metastasis

ABSTRACT

Introduction

Melatonin, originally isolated from the mammalian pineal gland, was subsequently identified in many animal cell types and in plants. While melatonin was discovered to inhibit cancer more than 5 decades ago, its anti-cancer potential has not been fully exploited despite its lack of serious toxicity over a very wide dose range, high safety margin, and its efficacy.

Areas covered

This review elucidates the potential mechanisms by which melatonin interferes with tumor growth and metastasis, including its ability to alter tumor cell metabolism, inhibit epithelial-mesenchymal transition, reverse cancer chemoresistance, function synergistically with conventional cancer-inhibiting drugs while limiting many of their side effects. In contrast to its function as a potent antioxidant in normal cells, it may induce oxidative stress in cancer cells, contributing to its oncostatic actions.

Expert opinion

Considering the large amount of experimental data supporting melatonin’s multiple and varied inhibitory effects on numerous cancer types, coupled with the virtual lack of toxicity of this molecule, it has not been thoroughly tested as an anti-cancer agent in clinical trials. There seems to be significant resistance to such investigations, possibly because melatonin is inexpensive and non-patentable, and as a result there would be limited financial gain for its use.

KEYWORDS:

• Cancer metastasis
• chemoresistance
• epithelial-mesenchymal transition
• free radicals
• glycolysis
• melatonin
• oxidative phosphorylation
• Warburg metabolism

Article highlights

• Melatonin is a highly versatile molecule since it functions as an antioxidant in normal cells and as a pro-oxidant in cancer cells.

• Melatonin’s pro-oxidative action in cancer cells is one means by which melatonin kills cancer cells.

• Melatonin reverses Warburg-type metabolism in cancer cells and converts them to a more normal phenotype.

• Melatonin prevents the epithelial-mesenchymal transition of cancer cells thereby inhibiting the progression of cancer.

• Melatonin reverses chemo- and radio-resistance of cancer cells, making them more vulnerable to conventional drugs.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper received no funding.