Melatonin attenuates hydrogen peroxide toxicity in MCF7 cells only at pharmacological concentrations.
Melatonin is proposed to be oncostatic in mammary tissue, and one mechanism by which this hormone may elicit its possible oncostatic effect is as an oxygen radical scavenger. Therefore, we examined melatonin's abilities to act as an oxygen radical scavenger at physiological or pharmacological concentrations. Hydrogen peroxide at 400 microM killed 97% of treated MCF7 cells within 8 h, and following melatonin at 10(-5) and 10(-4) M concentrations only 76 and 64% of cells, respectively, were killed by hydrogen peroxide. However, melatonin at lower concentrations (10(-7) M) did not protect MCF7 cells. Moreover, pretreatment with melatonin (10(-5) or 10(-7) M) prior to hydrogen peroxide stress offered no further efficacy, and pretreatment with melatonin followed by the withdrawal of melatonin eliminated its protective effect from hydrogen peroxide toxicity. These findings indicate that melatonin acts directly as an antioxidant and does not stimulate antioxidant defenses in MCF7 cells that protect against hydrogen peroxide. Glutathione levels were examined to substantiate this hypothesis and were not altered by melatonin treatment. In conclusion, melatonin is an excellent oxygen radical scavenger at pharmacological concentrations, but not at physiological concentrations. Thus, loss of melatonin is unlikely to be important in oxidative scavenger mechanisms in human mammary cells.
Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, 27709, USA.
W S
WS
Baldwin
J C
JC
Barrett
D000975:Antioxidants / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000473:pathology*; D002470:Cell Survival / Q000187:drug effects; D004347:Drug Interactions; D005260:Female; D016166:Free Radical Scavengers / Q000494:pharmacology*; D006801:Humans; D006861:Hydrogen Peroxide / Q000633:toxicity*; D008550:Melatonin / Q000494:pharmacology*; D016877:Oxidants / Q000633:toxicity*; D014407:Tumor Cells, Cultured
D000975:Antioxidants; D016166:Free Radical Scavengers; D016877:Oxidants; D006861:Hydrogen Peroxide; D008550:Melatonin