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Published on: July 30, 2016
Antioxidant activity of melatonin in Chinese hamster ovarian cells: changes in cellular proliferation and
Rosa M Sainz1, Juan C Mayo, Dun-Xian Tan
1Department 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.
Abstract:
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 Its effect is a reversible phenomenon that disappeared when melatonin was withdrawn from the culture medium.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.
Insights
Melatonin and antioxidants like resveratrol and vitamin E inhibit cancer cell growth. These compounds alter cell cycle and morphology, suggesting the cellular redox state influences transformation.
Area of Science:
- Biochemistry
- Cell Biology
- Oncology
Background:
- Melatonin is an endogenous molecule with antioxidant and free radical scavenging properties.
- Antioxidants play a role in cellular processes, including proliferation and transformation.
Purpose of the Study:
- To investigate the antiproliferative effects of melatonin and other antioxidants on transformed Chinese hamster ovarian (CHO) cells.
- To explore the impact of these compounds on cell cycle, morphology, and intracellular redox state.
Main Methods:
- Cell proliferation assays were performed on CHO cells treated with melatonin, resveratrol, and vitamin E.
- Flow cytometry was used to analyze cell cycle distribution (G0/G1, S, G2/M phases).
- Morphological changes and intracellular glutathione (GSH) levels were assessed.
Main Results:
- Melatonin demonstrated dose- and time-dependent antiproliferative effects on CHO cells.
- Resveratrol and vitamin E mimicked melatonin's inhibitory effect on cell proliferation.
- Melatonin treatment led to cell cycle redistribution, increased G0/G1 and G2/M phases, and reduced S-phase.
- Melatonin and trolox induced morphological changes towards a spindle-shaped, fibroblast-like appearance, which was reversible.
- GSH levels increased post-melatonin treatment, but GSH synthesis blockade did not negate the antiproliferative effect.
Conclusions:
- Melatonin and other antioxidants exhibit antiproliferative and differentiation-inducing effects on transformed CHO cells.
- The observed effects are linked to alterations in the intracellular redox state.
- Cellular redox state modulation may be a key mechanism in antioxidant-induced cellular transformation.
