Antioxidant activity of melatonin in Chinese hamster ovarian cells: changes in cellular proliferation and differentiation.
Melatonin is an endogenously generated molecule with free radical scavenging and antioxidant properties. Here, we studied the antiproliferative role of melatonin and other antioxidants on transformed Chinese hamster ovarian cells. Melatonin reduces cell proliferation in a dose- and time-dependent manner. Natural antioxidants which appear in edible plants including resveratrol and vitamin E mimicked the effect of melatonin. Flow cytometer analysis revealed that melatonin treatment reduces the number of cells in S-phase and increases cells in both G0/G1 and G2/M gaps. In addition, melatonin, as well as trolox, caused a clear morphological change by inducing the cells to become spindle shaped and fibroblast-like. Its effect is a reversible phenomenon that disappeared when melatonin was withdrawn from the culture medium. GSH levels are increased after melatonin treatment but pharmacologically blockade of GSH synthesis did not abolish melatonin's antiproliferative effect. Reduction of cell proliferation and the apparent induction of cell differentiation overlapped with melatonin's ability to change the intracellular redox state of CHO cells. We conclude that the cellular redox state may be involved in cellular transformation caused by antioxidants such as melatonin and trolox.
Sainz
Rosa M
RM
Department of Cellular and Structural Biology, Mail Code 7762, University of Texas Health Science Center, San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229-3900, USA.
Mayo
Juan C
JC
Tan
Dun-Xian
DX
Lopez-Burillo
Silvia
S
Natarajan
Mohan
M
Reiter
Russel J
RJ
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001205:Ascorbic Acid / Q000494:pharmacology; D016466:CHO Cells; D002454:Cell Differentiation; D002455:Cell Division; D002478:Cells, Cultured; D002839:Chromans / Q000494:pharmacology; D004396:Coloring Agents / Q000494:pharmacology; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D016193:G1 Phase; D016195:G2 Phase; D005978:Glutathione / Q000378:metabolism; D019803:Glutathione Disulfide / Q000378:metabolism; D008938:Mitosis; D010084:Oxidation-Reduction; D017382:Reactive Oxygen Species; D016192:Resting Phase, Cell Cycle; D000077185:Resveratrol; D016196:S Phase; D013267:Stilbenes / Q000494:pharmacology; D013778:Tetrazolium Salts / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology; D013997:Time Factors; D014343:Trypan Blue / Q000494:pharmacology
D000975:Antioxidants; D002839:Chromans; D004396:Coloring Agents; D017382:Reactive Oxygen Species; D013267:Stilbenes; D013778:Tetrazolium Salts; D013844:Thiazoles; C022616:thiazolyl blue; D005978:Glutathione; D014343:Trypan Blue; D001205:Ascorbic Acid; D000077185:Resveratrol; C010643:6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid; D019803:Glutathione Disulfide