Intracellular redox state as determinant for melatonin antiproliferative vs cytotoxic effects in cancer cells

Ana M. Sánchez-Sánchez, Vanesa Martín, Guillermo García-Santos, Jezabel Rodríguez-Blanco, Sara Casado-Zapico, Santos Suarez-Garnacho, Isaac Antolín, Carmen Rodriguez

Research output: Contribution to journalArticlepeer-review

64 Scopus citations


Melatonin is an endogenous indolamine, classically known as a light/dark regulator. Besides classical functions, melatonin has also showed to have a wide range of antitumoral effects in numerous cancer experimental models. However, no definite mechanism has been described to explain the whole range of antineoplasic effects. Here we describe a dual effect of melatonin on intracellular redox state in relation to its antiproliferative vs cytotoxic actions in cancer cells. Thus, inhibition of proliferation correlates with a decrease on intracellular reactive oxygen species (ROS) and increase of antioxidant defences (antioxidant enzymes and intracellular gluthation,GSH levels), while induction of cell death correlates with an increase on intracellular ROS and decrease of antioxidant defences. Moreover, cell death can be prevented by other well-known antioxidants or can be increased by hydrogen peroxide. Thus, tumour cell fate will depend on the ability of melatonin to induce either an antioxidant environmentrelated to the antiproliferative effect or a prooxidant environment related to the cytotoxic effect.

Original languageEnglish (US)
Pages (from-to)1333-1341
Number of pages9
JournalFree Radical Research
Issue number11-12
StatePublished - Nov 2011
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biochemistry


  • Cancer
  • Cell death
  • Melatonin
  • Proliferation
  • Redox state


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