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Published on: September 7, 2013
Melatonin decreases cell proliferation and transformation in a melatonin receptor-dependent manner
M P Jones1, M A Melan, P A Witt-Enderby
1Department of Pharmacology and Toxicology, Duquesne University, Pittsburgh, PA 15282, USA.
Abstract:
There are conflicting claims for the role of melatonin in oncogenesis. In addition, the mechanism(s) underlying melatonin's effects in oncogenic processes is (are) unknown. In this study, the effects of melatonin exposure on cell proliferation and transformation were assessed in NIH3T3 cells transfected with either the human mt(1) (NIH-mt1) or MT(2) (NIH-MT2) melatonin receptors. The effects of melatonin exposure on proliferation was assessed by direct cell counts and [(3)H]thymidine uptake assays. The effect of chronic melatonin pretreatment on transformation was assessed by focus assays. In both NIH-mt1 and NIH-MT2 cells, melatonin pretreatment decreased cell proliferation and transformation. Control (NIH-neo) cells did not show this effect. However, as revealed by the [(3)H]thymidine uptake assays, an increase in DNA synthesis occurred in NIH-mt1 cells, whereas no increase occurred in the NIH-MT2 or NIH-neo cells. Upon examination of melatonin receptors, a decrease in the function of both mt(1) and MT(2) receptors occurred. These data suggest that perhaps an attenuation of receptor-mediated processes are involved in the anti-proliferative and anti-transformation capabilities of melatonin in NIH3T3 cells. In addition, based on the [(3)H]thymidine assays, receptor mediated signal transduction mechanisms may slow the growth of cells via actions on the cell cycle. The results from this study shed new insight on the putative mechanisms underlying melatonin's effects on cell proliferation and transformation and lends support for a protective role of melatonin in oncogenesis.
Insights
Melatonin exposure reduced cell proliferation and transformation in NIH3T3 cells with melatonin receptors. This suggests melatonin may have a protective role against cancer by influencing cell cycle regulation.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- Conflicting evidence exists regarding melatonin's role in oncogenesis.
- The precise mechanisms of melatonin's influence on cancer development remain largely unknown.
Purpose of the Study:
- To investigate the effects of melatonin on cell proliferation and transformation.
- To elucidate the underlying mechanisms involving melatonin receptors (MT1 and MT2) in NIH3T3 cells.
Main Methods:
- NIH3T3 cells expressing human MT1 or MT2 receptors were used.
- Cell proliferation was assessed via cell counts and [3H]thymidine uptake.
- Cell transformation was evaluated using focus assays after melatonin pretreatment.
Main Results:
- Melatonin pretreatment decreased cell proliferation and transformation in NIH-mt1 and NIH-MT2 cells.
- Increased DNA synthesis was observed in NIH-mt1 cells, but not in NIH-MT2 or control cells.
- A decrease in the function of both MT1 and MT2 receptors was noted.
Conclusions:
- Melatonin's anti-proliferative and anti-transformation effects may involve attenuated receptor-mediated processes.
- Receptor-mediated signal transduction pathways might slow cell growth through cell cycle modulation.
- These findings support a potential protective role for melatonin in oncogenesis.
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