A new promising role of melatonin in promoting tumor necrosis factor toxicity in cancer cells

Rosa M. Sainz, Juan C. Mayo, Dun Xian Tan, Russel J Reiter

Research output: Chapter in Book/Report/Conference proceedingChapter


Melatonin, a neuroindole mainly produced by the pineal gland, has antioxidant, antiproliferative and anti-inflammatory properties which can be responsible to its beneficial effects on human health. It is well known that melatonin serum levels are reduced in cancer patients since late 80'ies and its role on the growth of cancer cells has been clearly demonstrated. Melatonin directly inhibits the growth of several cell types from diverse embryological origins including breast, prostate, melanoma, lung, kidney or brain; additionally, melatonin is a modulator of the immune function. Physiologically, melatonin administration results in a functional enhancement of immune cells which might play a key role against cancer cells in vivo. In fact, there is a direct crosstalk between the pineal gland and the immune system in several ways. Previous data suggest that the increase in circulating tumor necrosis factor-alpha (TNFα), after a defense response transiently blocks nocturnal melatonin production. In fact, the transcription of arylalkylamine-N-acetyltransferase, the rate-limiting enzyme in melatonin biosynthesis, together with the synthesis of the melatonin precursor N-acetylserotonin, was inhibited by TNFα. It is also clear that cytokine production caused by infection or inflammation, including TNFα, is reduced by melatonin pretreatment. The remarkable ability of TNFα to inhibit the growth of malignant tumor cells is unfortunately limited by its systemic toxicity. New strategies are being tested in order to reduce TNFα toxicity without losing its antitumor efficiency. On the other hand TNFα, induced by a wide range of pathogenic stimuli induces other inflammatory mediators and proteases that act as tumor promoters. The role of TNF in cancer has been linked to all steps of carcinogenesis including carcinogenesis, cellular transformation, promotion, survival, proliferation, angiogenesis and metastasis and how the cytokine works in this intricate link is actually a matter of debate. Since melatonin has been claimed to prevent the toxicity of several anticancer drugs and more recently, to enhance the toxicity of TNFα in cancer cells, we will discuss here the innovative idea of the employment of melatonin in combination with TNFα in cancer treatments. The possible use of melatonin in preventing the toxicity of TNFα without losing its antitumor properties as well as its capacity to promote ability to kill cancer cells especially resistant to TNFα treatment is an idea which needs to be deeply explored.

Original languageEnglish (US)
Title of host publicationTumor Necrosis Factor
PublisherNova Science Publishers, Inc.
Number of pages7
ISBN (Electronic)9781616682767
ISBN (Print)9781607417088
StatePublished - Jan 1 2009

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)


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