title: Intracellular redox state as determinant for melatonin antiproliferative vs cytotoxic effects in cancer cells.
abstract: 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 environment--related to the antiproliferative effect or a prooxidant environment related to the cytotoxic effect.
authors.affiliation: Departamento de Morfología y Biología Celular, Facultad de Medicina, Universidad de Oviedo, Oviedo, Spain.
authors.forename: Ana M
authors.initials: AM
authors.lastname: Sánchez-Sánchez
authors.forename: Vanesa
authors.initials: V
authors.lastname: Martín
authors.forename: Guillermo
authors.initials: G
authors.lastname: García-Santos
authors.forename: Jezabel
authors.initials: J
authors.lastname: Rodríguez-Blanco
authors.forename: Sara
authors.initials: S
authors.lastname: Casado-Zapico
authors.forename: Santos
authors.initials: S
authors.lastname: Suarez-Garnacho
authors.forename: Isaac
authors.initials: I
authors.lastname: Antolín
authors.forename: Carmen
authors.initials: C
authors.lastname: Rodriguez
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D005434:Flow Cytometry; D005978:Glutathione / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008550:Melatonin / Q000494:pharmacology*; D009369:Neoplasms / Q000378:metabolism*; D010084:Oxidation-Reduction / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D017382:Reactive Oxygen Species; D005978:Glutathione; D008550:Melatonin